Unit 1 Flashcards
membrane glycoproteins are oriented in the ER membrane with their carbs on the ____ side of the membrane
lumenal
enzyme that attaches carbs to Asn residues in proteins
oligosacharyltransferase
blood type allele encoding non functional enzyme
O
glycoprotein component of mucus
mucins
endoglycosidases remove ___ from glycoproteins
carbs
site of glycoprotein degradation
lysosome
carbs attached to proteins Ser and Thr residues are:
O linked
a function of mucus secretion
lubrication, protection from noxious substances
O blood group allele relative to A and B
recessive
protein with oligosaccharides attached
glycoprotein
diseases caused by defects in proteoglycan degradation
mucopolysaccharidoses
enzyme that cleaves bonds between sugars
glycosidase
ABO blood group antigens are oligosaccharide components of glycoproteins and ____
glycolipids
enzymes that cleave proteins into aa’s
proteases
membrane glycoproteins are oriented in the plasma membrane with their carbs on the ____ side of the membrane
EC
linear or branched polymer of sugars
polysaccharides
encoded by the ABO gene locus
glycosyltransferase
protects epithelial cells from noxious substances
mucins
sugar polymer containing a repeating disaccharide
glycosaminoglycan
Cys residues in mucins allow them to
polymerize
protein with glycosaminoglycan chains attached
proteoglycan
individuals with AB blood have alleles that are
codominant
O linked glycosylation occurs here
Golgi
individuals with O blood are considered universal ____
donors
failure to degrade glycosaminoglycans
mucopolysaccharidosis
where and how are glycoproteins degraded in the cell
lysosomes with hydrolases
what chemical property of glycosaminoglycans allows them to form lubricants and gels
hydrophilic, strongly - charge due to sulfates and carboxyl groups, attract water
where are mucins found
GI, resp, genitourinary tracts
synthesis of N linked glycoproteins
occurs in ER co translationally
added as a block of sugars
synthesis of O linked glycoproteins
in Golgi post translationally
added one at a time
what class of enzyme is responsible for adding sugars to O linked glycoproteins
glycosyltransferases
what is the structural difference between a glycoprotein and a proteoglycan?
glycoprotein–no serial repeat, mostly protein
proteoglycan–serial repeat, mostly sugar
oligosaccharide
3-15 sugars covalently bound in linear or branched chain (eg ABO blood group antigens)
polysaccharide
long linear or branched polymer of sugars (eg glycosaminoglycans, glycogen, starch)
glycosidase
cleaves glycosidic bond (b/w two monosaccharides)
glycosyltransferases
form glycosidic bonds
oligosaccharyltransferase
transfers a pre-formed oligosaccharide from its lipid anchor to an appropriate Asn residue in a polypeptide during N linked glycosylation in the ER
linear polymer of a repeating disaccharide unit with many negative charges on carboxyl and sulfate groups, form gels
glycosaminoglycan
Inclusion cell disease
defect adding M6P tag on lysosomal hydrolases
digestion of obsolete cell parts
autophagy
return to a different plasma membrane domain in a polarized cell
transcytosis (antibody transfer via breastmilk)
uptake of cholesterol from blood to make new membranes
receptor mediated endocytosis
defective LDL receptors so cholesterol uptake is blocked and builds up in blood, leads to heart attack
familial hypercholesterolemia
_____ exocytosis pathway: all proteins passing through the Golgi will enter this pathway unless directed elsewhere by a specific signal, vesicles bud from trans Golgi and fuse with plasma membrane, operates continuously
default
_____ exocytosis pathway: specialized secretory cells, use secretory vesicles, only in response to an EC signal
regulated
most cells have a thick layer of carbohydrate on their cell surface known as:
glycocalyx
enzyme that removes the carb from the protein
endoglycosidase
where O linked sugars are built
Golgi
trans Golgi sorts into these three destinations:
lysosome, plasma membrane, secretory vesicle
where N linked oligosaccharides are modified
Golgi
entry face of ER
cis
exit face of Golgi
trans
determinant of cell shape
cytoskeleton
organelle contiguous with nuclear envelope
ER
cell’s permeability barrier
plasma membrane
component of thin filaments
actin
ribosomal RNA synthesis site
nucleolus
protein degradation signal
ubiquitin
toxin clean up site
peroxisome
protein synthesis machines
ribosome
chromosome home
nucleus
mtDNA shape
circular
microtubule organizing center
centrosome
process that produces most of a cell’s ATP
ox phos
worn out organelles are digested here
lysosome
proteins synthesized in ER are modified in
Golgi
ATP generating powerplants
mitochondria
structures that form poles of the mitotic spindle
centrioles
double membrane protecting the genome
nuclear envelope
cell interior minus nucleus
cytoplasm
sorting station for endocytosed material
endosome
cytoskeletal element that arranges organelles
microtubules
extensively folded mitochodrial membrane forms
cristae
sea in which organelles reside
cytosol
lysosomal enzymes work best at __ pH
low
small organelles containing enzymes involved in oxidative reactions that break down lipids and destroy toxic molecules
peroxisomes
responsible for the transcription and processing of rRNAs and for assembly of ribosomal subunits
nucleolus
cylindrical protein degradation machines located in the cytoplasm
proteasomes
subunit for microtubule assembly
tubulin dimer
nucleotide bound to subunit of microtubule
GTP
cytoskeletal element most important for changes in cell shape
actin based microfilaments
filaments that provide strength to axons in the nervous system
neurofilaments
neurofilaments are a special type of
intermediate filament
centrosomes are assembly sites for
microtubules
kinesins move toward the __ ends of microtubules
+
dyneins carry ___ in a cilium
doublet microtubules are both track and cargo in cilium (so they can bend)
why is ciliary assembly essential for vision
rod and cone
cytoskeletal element with no structural polarity, not used as motility tracks, high tensile strength
intermediate filaments
specific enzyme defect produces a metabolic block, accumulation of substrate, deficiency of product
inborn error of metabolism
three distinct phenotypes from mutations of a single gene
phenotypic heterogeneity
mutations in different genes lead to same clinical phenotype
locus heterogeneity
stage in mitosis when chromosomes separate
anaphase
stage when chromosomes are best visualized
metaphase
nondisjunction during meiosis I results in daughter cells that are:
2-heterodisomic for A1 and A2
2-nullosomic for A1 and A2
nondisjunction in meiosis II results in daughter cells that are
2-normal
1-isodisomic A2 and A2
1-nullosomic for A
phase of recombination
prophase
stage of reductive division
anaphase I
meiosis of oocytes completed after
fertilization
primary oocyte arrested in ___ until ___
prophase I, ovulation
nucleotide
sugar, base, phosphate grp
nucleoside
sugar, base
bases with one ring
pyrimidines, CUT
bases with two rings
purines, AG
differentiation between A and G
G =O (big “GUst of AIR on my way to work”)
A does not have it
how to remember T
Tom does meth
how to remember C
Amy is a sight to see
number of base pairs per turn
10.5
angstroms per turn of B DNA
34A
base pairing: instead of anti conformations, bases are syn/anti, forms triple helix
hoogsteen
DNA is ___ stable at high pH
less
parts of chromosome responsible for accurate segregation of sister chromatids after chromosome replication, rich in ___ base pairs
centromeres, AT
telomeres are rich in ___ base pairs
GC
chromatin used for transcription
euchromatin
silenced chromatin
heterochromatin
enzyme that cuts strands to relieve topological stress
topoisomerase
attached to nuclear envelope, provides support and attached to chromatin
lamina
process that causes lamina disassembly during cell division
phosphorylation
Ran GAP is on the ___ side of the nucleus with higher concentrations of ___
cytoplasmic, GDP
Ran GEF is on the ___ side of the cell with higher concentrations of ___
nuclear, GTP
___ molecules are exported from the nucleus using Ran
RNA
___ molecules are transported into the nucleus using Ran
protein
4-8 aa’s on a protein recognized by importin
nuclear localization signal
in the nucleolus, DNA in the ____ is not being transcribed
fibrillar center
in the nucleolus, rRNA molecules are being synthesized in this compartment
Dense Fibrillar Component
in this part of the nucleolus, there are maturing ribosome precursors
A Granular Component
rRNA precursor strand for ribosome synthesis
45 S
components of the small ribosomal subunit
18s rRNA
components of the large ribosomal subunit
5.8s, 28s, and 5s from elsewhere
test ribosomal translation before leaving nucleus
pioneering
mobile DNA elements
transposons
copies of true genes
pseudogenes
parts of DNA that code for product
exons
parts of DNA that are removed
introns
histone octomer contains ___
H2A, H2B, H3, H4
30nm fiber is held together by which histone
H1
use of N-terminal tail domains on histones
Histone code, post translational modifications (acetylation, methylation) which alter local chromatin structure and therefore gene expression
part of the nucleus composed of proteins, provides structure and organization, chromosomes in it have distinct territories
nuclear matrix
how chromosomes are attached to the matrix
MARs matrix associated regions
autoimmune disease, body makes antibodies to own nuclear antigens
sytemic lupus erythmatosus
cancer caused by mutation in nuclear PML protein
acute promyelocytic leukemia
mutation in SMN (survival of motor neurons) part of protein involved in RNA processing
spinal muscular atrophy
genes encoded on acrocentric chromosome stalk arms
for rRNA
capped telomere on acrocentric short arm
satellite
normal variation in chromosome banding
chromosome polymorphism
number of complete sets of chromosomes N, 2N, 3N
euploidy
gain or loss of chromosomes less than a complete complement
aneuploidy
how to get aneuploidy
meiotic OR mitotic nondisjunction in anaphase I
normal embryo with mitotic error that gives rise to some cells with three copies of chromosome, acquired
mosaicism
how to get testes, androgen
TDF/SRY
females have ___ of Müllerian ducts
proliferation
males have ____ of Wolffian ducts
proliferation
when does X inactivation occur
3-7 days into development
how many Barr bodies does a cell have
number of X chromosomes - 1
is x inactivation random or nonrandom
random (if non random due to structural abnormality, females could express X linked diseases)
how are X chromosomes inactivated
epigentically, with methylation
____ region of chromosome escapes X inactivation
psueoautosomal
phase when DNA replicates
interphase
Meselson-Stahl experiment showed that DNA replication is __
semi conservative
what stops DNA from replicating throughout cell cycle
cyclin dependent kinase
a mutation in MMR gene leads to this phenotype, causes this disease
mutator phenotype, non polyposis colon cancer
polymerases used in event of a DNA lesion to minimize damage
error prone DNA polymerase, by template switching or hopping over it
defect in replication stress response can lead to these two diseases
AT, Bloom Syndrome
how does AZT work
chain terminator, nucleoside analog
how does camptothecin work
targets Topoisomerase I
environmental DNA damaging agents
mutagens
how to repair template independent damage
direct reversal by photolyase
how to repair single strand DNA damage
BER, MMR, NER
how humans repair double strand breaks
non homologous end joining
disease caused by defective NER
xeroderma pigmentosum
head group of membrane lipids contains
OH group
longer and more saturated chains are ___ fluid (more/less)
less
cis double bond causes kinks, resulting in ___ fluid membrane (more/less)
more
characteristics of cholesterol
lots of rings, only hyrophilic structure is the OH group on the end
sphingosine backbone with a sugar attached to primary OH group
glycolipid
hydrophilic part of sphingomyelin
phosphoryl choline
primary force driving formation of lipid bilayers
hydrophobic effect
effect of cholesterol on membrane fluidity
overall, decreases, but increases fluidity at border of cholesterols bc chains can’t organize
lipid bilayer is most impermeable to ____
ions
four ways drugs can enter cells
passive diffusion, hijack transporters, liposome delivery, protein transduction
how to remove integral membrane protein
harsh detergent
lipid rafts are involved in _____
signal transduction, protein sorting and recognition, viral entry or exit from cell
actin monomer binds _ and _
Mg and ATP
____ form by self assembly of actin monomers
microfilaments
adding units bound to ATP at one end, losing units bound to ADP at other end of microfilament
treadmilling
combination of plasma membrane and underlying mesh of crosslinked actin filaments
cell cortex
parallel, unbranched microfilaments
filopodia
branched, extensions of cell membrane, ARP mediated, involved in migrating cell
lamellipodia
contractile ring of microfilaments found in a ____ cell
dividing
type of myosin that doesn’t form filaments. Monomeric, stand alone vesicle vector. Tails associate with membranes.
Myosin I
type of myosin that assembles into bipolar filaments, heads face opposite directions, doesn’t move
Myosin II
what activates myosin
phosphorylation of associated proteins (caused by change in Ca concentration)
myosin regulation is known as ____
thick filament based regulation
regulation of muscle contraction is known as
thin filament (or actin) based regulation, faster
troponin’s role
positions tropomyosin on actin filament. binds to Ca, tropomyosin, and actin
role of tropomyosin
covers (or uncovers, in presence of Ca) myosin binding site on actin
how Ca is released into muscle cell
AP to transverse tubules to SR to voltage gated channels, releases Ca
myosin pulls toward the __ end of the actin
+
how is the sarcomere array anchored to the plasma membrane
dystrophin
the ____ is divided into sarcomeres
myofibril
how are myofibrils connected to each other
desmin intermediate filaments
how is myosin held in place in the sarcomere
titin
what separates myofibrils
SR
myosin during rigor state
bound to actin, NO ATP
myosin during release
ATP BOUND, myosin head lowers affinity for actin
myosin when cocked
ATP hydrolysis causes translocation of myosin head, weak affinity for actin
myosin during Force Generating step of muscle contraction
phosphate dissociates, increased affinity of myosin for actin, activates power stroke
myosin during attached phase of muscle contraction
ADP dissociates as myosin head returns to original position
47, XXX
female, often undected, fully fertile, generally have chromosomally normal children
47, XYY
male, often undetected, normal, due to a nondisjunction error in the father
47, XXY
Klinefelter syndrome. Male with some female characteristics bc of week of development before X was inactivated. post pupertal hypogonadism, infertility
45, X
Turner syndrome. female, short stature, webbed neck in utero, usually infertile. 10% are mosaics, ratio of normal to abnormal determines severity (and a 46XY/45X can be either male or female. fine for males, detrimental for females)
XY female
androgen insensitivity, mutation of androgen receptor gene on long arm of X chromosome, +TDF/SRY, infertile
XX “Male”
can be treated, due to biochemical imbalance, virilization of female fetus that has congenital adrenal hyperplasia, lack of enzyme that allows androgens to build up in the body, male appearing infant
XX male is due to
an error in recombination during male meiosis. Balanced translocation with no clinical significance unless father passes X chromosome onto child
terminal deletion, Greek Warrior’s helmet facial expession
Wolf Hirschhorn Syndrome
parents are normal but child has a deletion
de novo interstitial deletion
a duplication of the critical region of chromosome 21 can result in
Down Syndrome
reciprocal translocation risk
for chromosomally abnormal children
balanced translocation carrier with no risk to children
alternate segregation
balanced translocation carrier with risk to children
adjacent 1 segregation, adjacent 2 segregation, 3:1 segregation
translocation variant of standard reciprocal translocation, occurs only between two acrocentric chromosomes, only 45 total chromosomes but full content of DNA. Increased risk of ____
Robertsonian, nondisjunction
inversion when breaks occur on opposite sides of the centromere
pericentric
inversion on same side of centromere
paracentric, usually benign
An alteration in the DNA which has a population frequency less than 1%
rare genetic variant
Tay Sachs method of inheritance
autosomal recessive
presence in males of a single allele at X linked loci is:
hemizygosity
associated with rare autosomal recessive disorders
consanguinity in the parents of a proband
a mosaic individual has two or more cell lines of different genotypes derived from a ___ zygote
a single zygote
all or none expression a genetic disease genotype
penetrance
the occurrence together in a population of two or more alleles, each at a frequency greater than 1%, so that the heterozygote frequency is at least 2%
polymorphism
MOI hemophilia A
XLR
MOI CF
AR
MOI a-1 Antitrypsin def
AR
MOI DMD
XLR
MOI Tay Sachs
AR
MOI sickle cell
AR
MOI a and B Thalassemia
AR
MOI HD
AD
MOI DM
AD
DM disease stands for
diabetes mellitus
the proportion of the phenotypic variance caused by additive genetic variance
heritability
traits that are influenced by environmental factors, the recurrence risk is higher the more family members that are affected, gene-environment interactions, the more severe the malformation the greater the risk
multifactorially determined traits
when an allele/mutation is at a frequency of 1% or greater (2% or more of individuals will carry at least one autosomal copy)
polymorphism
genes/loci close together on the same segment of chromosome are said to form____ which tend to travel together through meiosis
haplotypes
distance between genes measured in centiMorgans
recombination distance
one centiMorgan represents approximately ______ base pairs
1 million
one centiMorgan represents a __% chance of crossover
1%
term used to describe co-segregation as two loci tend to travel together through meiosis
Linkage Disequilibrium
in linkage studies, neutral/benign mutations _____ a gene (what kind of marker) are better than those _____ a gene
within (intragenic marker); flanking
a sibling of a known carrier with no affected siblings has a __ chance of being a carrier of an autosomal recessive mutation
half
mother of an affected son that follows Haldane’s Rule has a __ chance of being a carrier
2/3
phase is known when:
alleles at two loci are known to occur on the same homologous chromosome, alleles at two loci are known to occur on the opposite homologous chromosome, you can tell which haplotype came from which parent, haplotypes can be constructed
estimating the distance between the disease and the marker
If the recombination distance between the marker and the disease is 15cM, what is the real physical distance between the marker and the disease
the further apart, the more a two point recombination rate will underestimate the physical distance because of the increasing influence of double crossovers.
about 20 Megabase
if two loci are within 50cM of each other, they must/may not be on the same chromosome
must be on the same chromosome
three classes of mutations
linked extragenic markers, intragenic markers, disease causing-mutations
_____ binding of a ligand (signaling molecule) to a receptor protein on a cell induces a conformational change in the receptor, triggering changes in other molecules inside the cell
non covalent
receptor conformational change results in a change in ___ if the receptor is an enzyme, or a change in ____ for another molecule if the receptor lacks enzymatic activity
activity, affinity
molecules inside the cell that carry the signal away from the receptor
second messengers
the concentration of a signaling molecule depends on the rate at which new molecules ___ and the rate at which they are ____
appear, removed
rapid changes in signal strength require a (short/long) signal half life
short
cell responses to a particular signal depend on
signal molecule [ ]
number of available receptors
receptor affinity for signaling molecule
expression of tissue or cell type specific second messenger systems
long term changes in signaling molecule concentration often cause target cell ____
adaptation
ways to accomplish target cell adaptation
change number of available receptors, affinity of receptor for its ligand, response sensitivity of second messenger pathways to receptor activation
fewer receptors = (more/less) sensitive cell
less
the same type of receptor (can/does not) activate different second messengers in different cells
can
two signal molecules (may/may not) act through the same second messenger
may–a boost in the concentration of one signal makes the cell more sensitive to the other one
types of signaling that occur over short distances
autocrine, paracrine, synaptic
signals carried through bloodstream
endocrine
signals that originate outside the organism
sensory
endocrine signals in (low/high) concentrations with (low/high) affinity receptors
low concentration, high affinity receptors
neurotransmitters have (low/high) concentrations with (low/high) affinity receptors
high concentrations, low affinity
examples of small rapidly diffusing signal molecules with short half lives
NO, CO
what signal molecule regulates smooth muscle contraction
NO
how are hydrophobic molecules like steroids, retinoids, and thyroid hormones carried throughout the blood
binding proteins
eicosinoids
hydrophobic molecules that bind surface receptors, derived from phospholipids and include prostaglandins
short half lives, autocrine signals
action of anti inflammatories like cortisone and aspirin
inhibit synthesis of eicosinoids
examples of sensory signals
light, sound, chemicals (smells and tastes)
nuclear receptors are used for what kind of signals and what do they do
used for hormone binding
activate gene transcription
example of a carrier protein for hydrophobic signal molecules like steroid hormones
albumin
how are nuclear receptors activated
binding of ligand to receptor causes inhibitory complex to dissociate, thereby activating receptor and exposing its DNA binding site
nuclear _____ induced by hormone binding is a mechanism common to many nuclear receptor family members
translocation
genes activated by the hormone occupied receptor
primary response gene
amplification as a result of nuclear receptors happens at the level of (transcription/translation)
transcription
how do hydrophilic signals work? four main types
ligand-gated ion channels, enzyme-linked receptors, catalytic receptors, trimeric G-protein linked receptors
different types of ion channels (four)
voltage gated, mechanically gated, gated by extracellular ligands (primary signals), or intracellular ligands (secondary messengers)
the most common enzyme-linked receptors are those that stimulate membrane-associated:
tyrosine–specific protein kinases (such as the src kinase)
when a neurotransmitter binds to a receptor on the post synaptic cell, what change occurs in the post synaptic cell
change in membrane potential
signals that travel within a tissue
paracrine
when sensitivity of a cell to ligands is decreased after prolonged exposure
adaptation
eicosinoids bind (surface receptors/intracellular receptors)
surface receptors
role of heterodimer formation in steroid hormone signaling
heterodimeric transcription factors formed by nuclear receptors allow different cell types to respond differently to the same steroid hormone
each cell type can express a different partner to make a different heterodimer
phosphates may be added to the hyroxyl groups of which aa’s
serine, threonine, tyrosine
what does phosphorylation change on/for a protein
activity, conformation, new interaction site
how do you turn off a protein that is activated by phosphorylation
phosphatase
some G proteins hydrolyze GTP so slowly that they effectively remain “on” unless activated by a __
GAP
reactivation of the G protein requires the release of GDP and binding of GTP, which usually requires a ___
GEF
two classes of G proteins
trimeric, monomeric
signal-on state of a G protein
GTP bound
subunits of a trimeric G protein
alpha, beta, gamma
trimeric G protein subunit with the guanine nucleotide binding sites
alpha
the a/b/g-GDP trimer is (active/inactive)
inactive
trimeric G proteins are linked to the (cytosolic/extracellular) side of the plasma membrane by lipid tails
cytosolic
when the ligand binding site of a GPCR is occupied, a trimeric G protein can bind to the intracellular part of the receptor, which stimulates ______
GDP-GTP exchange
the GPCR (does/does not) bind directly to GTP
does not
after the a and b/g subunits of the trimeric G protein separate, they bind to and alter the activities of:
membrane associated enzymes or ion channels
events triggered by G protein activation depend mostly on which gene family the __ subunit comes from
alpha
the bound GTP is (slowly/quickly) hydrolyzed and the inorganic phosphate is released (slowly/quickly)
slowly, quickly
GDP dissociates (slowly/quickly) from the alpha chain of the alpha subunit in a trimeric G protein
slowly
activation of Gs family members stimulates ___ raising ___ concentrations
adenylate cyclase, cAMP
increased cAMP concentrations stimulate ___
PKA
PKA is a _______ kinase
serine/threonine
binding of alpha-s to adenylate cyclase also stimulates alpha-s ___ activity, shutting off the signal
GTPase
PKA structure: _ catalytic subunits and _ regulatory subunits
2, 2
if no cAMP is present, PKA catalytic subunits are _____ by the regulatory subunits
inhibited
cAMP interacts with which subunits of the PKA, and causes them to do what
regulatory, dissociate
how are cAMP levels lowered
phophodiesterase
what does GTP hydrolysis achieve for the Gs family of G proteins
lowers cAMP
activation of __ family members inhibits adenylate cyclase, reversing the effects of Gs (and alters K+ channel conductance in some cells)
Gi
activation of Gq family of trimeric G proteins does what?
stimulates phospholipase CB, which degrades membrane phospholipids
IP3 is made when phospholipase C cleaves phosphoinositol bisphosphate when Gq is activated. IP3 does what?
opens gated Ca++ channels in the ER
when IP3 releases Ca++ from the ER, what are stimulated?
CAM kinases
CAM kinases use ___, a small Ca++ binding protein, as a regulatory subunit
calmodulin
resting intracellular Ca++ concentrations are (low/high)
very low
activation of the Gq linked GPCR leads to activation of a myosin light chain kinase, a CAM kinase that _____ smooth muscle and non muscle myosin light chains, activating contraction
phosphorylates
DAG activates ___ by increasing its affinity for Ca++, which is required for ___ (same) activation
PKC
______ are tumor promoters–they irreversibly bind to and activate PKC, permanently stimulating a pathway involved in regulating cell division
phorbol esters
basic mechanism of receptor kinase activation
receptor dimerization causes autophosphorylation of tyrosine residues in the receptor itself and stimulates kinase activity
transphosphorylation
two subunits each act on each other–why dimerization is needed in tyrosine kinases
___ domains on cytoplasmic proteins bind to phosphotyrosine groups on the receptor
SH2
role of the ligand in tyrosine kinase activation
brings the domains together to form a dimer
how is the signal relayed by a tyrosine kinase?
intracellular signaling proteins bound to phosphorylated tyrosines carry the signal into the cell’s interior
examples of second messenger pathways of receptor tyrosine kinases
phospholipase C binds by its SH2 domain and stimulates IP3 and PKC pathway (same as Gq)
adaptor proteins indirectly activate monomeric G proteins of the ras family (GEF/GAP)
activated ras stimulates a MAP (mitogen activated protein kinase) cascade
MAP cascade
MAP kinases are mostly serine/threonine kinases with specificity for targets important in growth control including transcription factors that regulate cyclin genes, cyclin dependent kinase inhibitors
there is a (small/wide) range of tyrosine kinase diversity
wide range of diversity
tyrosine kinase receptors have been identified as the products of genes that are mutated in human ___
tumors
tyrosine kinase linked receptors
lacks kinase activity but dimerization stimulated by the ligand activates a separate protein tyrosine kinase associated with the receptor protein
example of tyrosine kinase linked receptors
JAK-STAT pathway
stimulation of __ activates a phospholipase, which cleaves PIP2 into IP3 and DAG. IP3 binds to ligand-gated ___ channels in the ER and releases __ (same) into the cytosol
Gq, Ca++
What are SH2 domains and what role do they play in signal transduction
SH2 domains bind to aa’s that include phosphorylated tyrosine residues. Through binding, they change the conformation of the SH2 domain protein and signal to the rest of the cell that a receptor tyrosine kinase has been activated.
how is PKA activated
cAMP through Gs
how is PKC activated
by DAG through Gq
how is CAM kinase activated
by calcium, through Gq or other signaling pathways that increase calcium concentrations
the phosphorylation of one receptor molecule by another after dimerization of the receptor which passes the signal from the EC domain to the cytoplasmic domain of the receptor
transphosphorylation
steps of GPCR’s that allows a signal to diffuse throughout the cell
cAMP and calcium
why have tyrosine kinase genes been identified as proto-oncogenes
they are involved in signaling pathways that regulate passage through the cell cycle. continuous activation can lead to uncontrolled cell division
which type of GPCR usually as the higher rate of spontaneous GTPase activity (monomeric or trimeric G proteins)
trimeric G proteins can self inactivate through GTP hydrolysis while monomeric G proteins generally require the activity of a GAP in order to shut off the signal
what are connective tissues primarily composed of
extracellular matrix
three parts of adhering (anchoring) junctions
transmembrane glycoprotein-interacts with proteins on adjacent cells or with proteins of the ECM
complex of proteins on the cytoplasmic face of the junction forming a plaque that mediates the association between the membrane protein and the cytoskeleton
cytoskeleton network-either actin or intermediate filaments
function of adhering (anchoring) junctions
maintain integrity of the tissue when subjected to mechanical stress (skin, muscles)
what would happen if adhering (anchoring) junctions didn’t have attachment to a cytoskeleton network
the cellular tissues would be unstable since the glycoproteins could not be pulled out of the lipid based (fluid) membrane
two types of microfilament based adhering/anchoring junctions
adherens (adhesion belts), focal adhesions/focal contacts
adherens junctions (adhesion belts) are a type of __-__ junction
cell-cell
what are the major transmembrane protein component of adherens junctions (adhesion belts)
cadherins
cadherins associate with identical cadherin molecules on neighboring cells via ___ interactions
homophilic
plaque proteins stabilize the link to the ___ cytoskeleton (adherens junctions/adhesion belts)
actin
in addition to providing strength, the positioning of adherens junctions towards the apical surface of cells allows for oriented contractions of the actin filaments to initiate an _____ of the ____ ___
invagination of the epithelial sheet, which can then pinch off to form a separate tube of epithelial cells
how is the neural tube formed during embryogenesis
invagination of epithelial cells to form a tube using actin filaments and same-oriented epithelial cells (adherens junctions)
epithelial sheets express _ cadherin while neural tube cells express _ cadherin
E, N
focal adhesions/focal contacts are a type of ___-___ anchoring junction
cell-matrix
transmembrane glycoproteins found in focal adhesions
integrins
focal adhesions are a type of (hetero/homo) philic type junction
heterophilic junction
____ adhesions are important in dynamic events such as cell motility in the context of cancer cell migration and metastasis
focal
focal adhesions require (extracellular/intracellular) Ca++
extracellular
adherens junctions (adhesion belts) require (extracellular/intracellular) Ca++
extracellular
cell-cell anchoring junction, cadherins are the major membrane component, homophilic interaction between cells, plaque proteins link cadherins to the intermediate filament cytoskeleton
desmosomes
cell-matrix anchoring junction with integrin as the major transmembrane glycoprotein component, link epithelial cells to underlying basal lamina in a heterophilic interaction
hemi-desmosomes
integrins associate in a (homo/hetero) philic way with ECM
hetero
basal lamina is a special type of
ECM
desmosomal disorders (two)
pemphigus: autoimmune to skin desmosomal cadherin causing destabilization of cell-cell interactions
empidermolysis bulosa simplex: defect in intermediate filament assembly causing loss of integrity of desmosomes and hemi desmosomes
functions of tight junctions
block paracellular transport (across sheets of epithelia) and promote transcellular transport (from gut to blood stream through epithelial cell)
tight junctions partition membrane proteins into correct regions of the cell membrane and thereby maintain cell ____
polarity
proteins composing the tight junctions (two)
claudin and occludin-homophilic interaction
tight junctions (do/do not) rely on the cytoskeleton for integrity
do not rely on it
gap junction function
communication between neighboring cells in electrically excitable cells (cardiac muscle)
protein component of gap junctions
connexin (six of them form a connexon)
small molecules can pass through gap junctions. this is important for setting up ____ gradients within epithelial sheets which can provide ___ information during embryogenesis
concentration, positional
gap junctions type of association homo philic/phobic
homophilic
gap junction regulation: high Ca++, low pH
gap junction is closed
gap junction regulation: low Ca++, high pH
Gap junction is open
____ cells generate the ECM in many connective tissues
fibroblasts
____ cells generate the ECM that forms cartilage
chondroblasts
____ cells generate the ECM that forms bone
osteoblasts
three major structural components of the ECM that contribute to the phenotype of connective tissues
fibrous proteins, bulky fillers, cross linker proteins
three types of fibrous proteins in connective tissues
fibrillar collagen (tensile strength), non fibrillar collagen (basal lamina, cannot form higher order fibrillar structures), elastin (allows stretching)
fibrillar collagen characteristics
post translational modifcations, pro collagen triple helix, secreted collagenases cleave off propeptides, form higher order structures
genetic disease associated with dysfunction in collagen synthesis/assembly, hyper extensible skin
Ehlers Danlos Syndrome
mutations in fibrillin gene are the cause of ____ syndrome, a condition that results in weak artery walls (severe cases-rupturing of the aorta)
Marfans Syndrome
characteristics of bulky fibers
complex proteoglycan molecule–protein backbone with serine residues, sugar side chains undergo carboxylation and sulfation so they have a (-) charge which attracts H2O and makes a gel
primary function of bulky fibers
to fill space and permit the movement of water soluble molecules and cells
cross linker proteins (fibroconectin and laminin) functions
link cellular tissue layers to connective tissue layers
fibroconectin is a dimer held together by disulfide bonds. It has binding sites for:
heparin, cell surface receptors (integrins), collagen (not type IV), fibrin, syndecan (focal adhesions)
lamin binds to __________ unlike fibroconectin
type IV collagen
two types of junctions that do not utilize interactions with the cytoskeleton
gap junctions and tight junctions
basal lamina is used for what function
molecular filter in the kidney
the basal lamina acts as a permeability barrier in the glomerulus, allowing the passage of ___ and blocking the loss of ____
small metabolites, blood proteins
a condition that results from environmental insult that mimics a Mendelian disease
phenocopies
mother is affected and so are all her children, of all genders
mitochondrial
Haldane’s rule applies when
X linked recessive, reduced fitness, no other family history (goes by the mother’s side)
X linked recessive affects
boys when mother is affected, girls when father is affected
pedigree showing evidence of germ line mosaicism in parent
unaffected male with two affected children by two different partners
SNP pros and cons versus microsatellites
SNPs are less informative but more stable than microsatellites
DMD seen in child but no deletion found in mother’s blood. fetus could still have a ___% chance of having it because the mutation could be in her ______
7%, germline
G1 cyclins are synthesized in G1 as regulatory subunits of ___
CDKs
non dividing cells usually stop in which phase of the cell cycle
G1
MAP kinase activity in G1 increases synthesis of ____ and blocks the action of __ and related inhibitor ___
cyclin subunits, p21 and p27
what proteins are synthesized during S phase of the cell cycle
histones
what duplicates in S phase but doesn’t separate until the start of mitosis
centrioles
what event in G2 phase blocks further transcription for the cell
chromosome condensation
what is the role of cohesins in the cell cycle, and when are they added
they are added during G2 and at the start of M
they help package chromosomes for mitosis by linking the replicated sister chromatids together until anaphase
the onset of mitosis is controlled by what enzyme’s activity
kinase
what motor protein crosslinks the microtubules during mitosis
kinesins
what is located at the primary constriction point of each duplicated chromosome during metaphase
kinetochores
unattached microtubules during metaphase are called ___ microtubules
astral
the trigger for the metaphase to anaphase transition is the tension on all kinetochores, which inhibits the activity of a _____ (enzyme)
kinase
when all kinetochores are under the same tension during metaphase, the _ _ _ becomes active and triggers separation of chromatids
Anaphase Promoting Complex APC
during telophase, the division of the cytoplasm begins with the assembly of a ___ ___
contractile ring
failure of cytokinesis after mitosis results in:
binucleated or multinucleated cell
most animal cells blocked in mitosis for prolonged periods undergo ____
apoptosis
checkpoints during the cell cycle
entry into mitosis (G2/M)
entry into S
exit from mitosis
a serine/threonine specific protein kinase that has no activity unless combined with a matching regulatory subunit
cyclin dependent kinase
inhibition of cdk’s
inhibitory phosphates
activation of mitotic cdk
add phosphates to two different places of the kinase subunit by two different kinases
inactivation of cdk
- cyclin subunit is ubiquitylated by an E3 ubiquitin ligase, targeting the cyclin subunit for proteolytic destruction by the proteosome
- the activating phosphate is removed from the kinase subunit
what is the role of the Anaphase Promoting Complex (2 roles)
ubiquitin ligase that turns off cyclin dependent kinases
promotes chromosome separation by activating the protease Separase
role of p53 in the cell cycle
stabilizes the protein against proteolytic degradation and activates it, inhibits cdks by increasing the concentration of proteins that bind to cdks and block their activity
new deoxynucleosides are only incorporated into DNA during the __ phase of the cell cycle
S
three major checkpoints in cell cycle
entry to M, G1/S border, metaphase to anaphase
what prevents DNA from being replicated more than once every cell cycle
origins of replications
what mitotic events occur before the nuclear envelope breaks down
chromosome replication, spindle elongation
the event that triggers cells to pass the metaphase/anaphase checkpoint and proceed through to the final steps of mitosis is:
tension on all kinetochores from bipolar microtubule movement
during the progression through the cell cycle, the molecule whose concentration/amount is most carefully controlled is:
nuclear genomic DNA
genetic defect in apoptosis
syndactyly
difference between cells undergoing apoptosis and necrosis
apoptosis: cells shrink then release small membrane bound apoptotic bodies that are phagocytosed by macrophages
necrosis: cells swell and burst, releasing their intracellular contents and frequently causing inflammation
when there is insufficient trophic factors and no phosphorylation of Bad, the cell:
undergoes apoptosis by cytochrome C which activates the caspase cascade
when there is sufficient trophic factor, Bad is phosphorylated and the cell:
can survive
causes of senescence
normal adult cells that have reached the end of their telomeres (telomerase not active)
protein important for blocking entry into S phase following DNA damage or when chromosomes have lost their telomeres
p53
growth factor that acts locally
platelet derived growth factor, present in blood serum
growth factor that acts systemically
erythropoietin
mechanism used by stratified epithelia to regulate cell proliferation
anchorage dependent cell growth
how cells know when to stop dividing during wound repair
density dependent growth inhibition (when cells touch each other they stop dividing)
cancer cells usually lack (four things)
growth factor dependence
anchorage dependence
cell-cell contact inhibition
do not become senscent
genes that encode normal cell proteins that function to stimulate cell growth and division
proto oncogene
oncogenes are ___ active proto-oncogenes
constitutively
how many alleles of a proto oncogene need to be mutated to affect cell growth
one
how many alleles of a tumor suppressor gene must be mutated for the gene to be inactivated
two
an inhibitor of gene transcripition. In its active state, ___ binds and sequester the transcription factor E2F. It is controlled by a cdk
Rb, retinoblastoma
how is Rb inactivated
phosphorylation
if p53 is damaged or missing, what will happen to a cell with damaged DNA
it will continue to divide
how does HPV cause cancer
produces two proteins that bind to p53 and Rb so cell can undergo unregulated division
how does SV40 virus cause cancer
produces large T antigen that binds both Rb and p53, sequestering those proteins and preventing them from regulating cell division
the conversion of pro caspases to caspases leads to:
apoptosis
___ levels of trophic factors in the developing brain prevent apoptosis
high
the kinase that phosphorylates the Rb protein, allowing E2F dependent transcription, can be best described as
a proto oncogene
the proportion of phenotypic variance caused by additive genetic variance
heritability
antibiotic resistance due to mutation is (a response/a preexisting selection factor) to the antibiotic
preexisting selection factor
the prophage pathway of transduction can give way to the lytic pathway via
an induction event caused by stress (virus knows it needs to get out of a stressed host)
five ways transposons contribute to genetic diversity
disrupting genes in which they land
altering the expression of neighboring genes
facilitating rearrangement of the bacterial chromosome through homologous recombination between transposon copies
by hopping into plasmids or bacteriophages and transferring their genes via these vectors to other bacteria
amplifying copies of antibiotic resistance genes
a mechanism by which bacterial transposons move that results in amplification
transposon is copied by DNA replication and inserted into a new site
type of transposon movement that does not result in amplification
non replicative transposition
cuts from its old site to move to a new site
number of possible gametes from each parent
2^n (n=23) due to independent assortment
genes involved in eukaryotic homologous recombination
RAD
how to retrotransposons move in humans
RNA intermediate
how do retrotransposons contribute to human genetic diversity (three ways)
disrupt gene function by insertion
affect expression of genes
create sites for illegitimate homologous recombination known as unequal crossovers
unequal crossovers created by retrotransposons create:
gene families (like the globin genes)
anchors cell membrane of muscle and stabilizes the cytoskeleton-plasma membrane interactions
dystrophin
deletion of the exons that code for the repeat of unequal crossovers leads to shorter forms of what protein in muscle
dystrophin, leads to muscular dystrophy
retrovirus genome
ssRNA
how were many of the known oncogenes discovered
they were tumor causing passengers on animal retroviruses
how is homologous recombination initiated
double strand DNA breaks
homologous recombination results in the (reciprocal/non reciprocal) exchange of genetic information between homologous chromosomes
reciprocal
the higher the Lod score the more likely the distance associated with it is ___
true
the smaller the theta associated with the maximum Lod, the (closer/further) the marker is to the disease gene
closer
knowing whether two alleles, at different loci, were inherited from the same parent
knowing phase
DMD is a large gene. What is the implication of that for intragenic markers?
Not as useful, still have to consider recombination
alleles at different loci are said to be in _____ when on the same chromosome (cis)
coupling
alleles at different loci are said to be in ____ when on opposite chromosomes (trans)
repulsion
