MCB Flashcards
What are the four types of cell-cell communication?
Endocrine
Paracrine
Neuronal
Contact-dependent
In what type of secretion does a cell secrete a signal that is recognized by its own receptors?
Autocrine signaling
What two major signaling pathways use GPCR’s?
1) Creates cAMP as 2nd messenger using adenyl cyclase as effector protein-> PKA(serine/threonine kinase), can be Gs or Gi
2) Gq activation, creates DAG and IP3 as 2nd messengers using phospholipase C (PLC) as effector protein -> activates PKC (serine/treonine kinase)
Emery-Dreifuss muscular dystrophy
-EMD and LMNA mutations
-Early childhood onset
-Contractures (joint deformities): restricted movement of elbows, ankles and neck
Muscle weakness
Heart problems
Dilated Cardiomyopathy
- 30 genes (LMNA rarely) cause fragile lamina
- Enlarged heart, arrhythmis, SOB, fatigue, syncope, swelling in hands/feet
Lipodystrophy
- LMNA mutations
- AD
- Fat loss in limbs, increased in face/neck/abdomen
Hutchinson-Gilford Progeria Syndrome
- LMNA mutations = abnormal lamin A= premature cell death
- AD
- Rapid aging, beginning in infancy
Spinal Muscular Atrophy
- SMN gene mutations = motor neuron death
- AR
- Four types
Type I spinal muscular atrophy
- aka Werdnig-Hoffman disease
- Evident at birth or very early
- Developmental delay, no support of head, cannot sit, breathing/swallowing problems
Type II spinal muscular atrophy
- Muscle weakness starting 6-12 mo.
- Cannot stand/walk unaided
Type III spinal muscular atrophy
- aka Kugelberg-Welander disease
- Milder features, develop in early childhood- adolescence
- Walking/ climbing stairs is difficult, usually require wheelchair later on
Type IV spinal muscular atrophy
- Sx after age 30
- mild/moderate PROXIMAL muscle weakness, tremor, twitch, breathing problems
Cystic Fibrosis
- CFTR mutation = abnormal chloride transporters= thick mucus
- AR
- Respiratory and pancreatic problems (decreased insulin and digestive enzymes)
Familial Hypercholesterolemia
- LDL receptor gene mutation = decreased cholesterol uptake
- AD
- Tendon xanthomas, xanthelasma, corneal arcus, premature atherosclerosis, angina
I-cell Disease (Mucolipidosis II) cause:
-GNPTAB gene mut. = abnormal N-acetylglucosamin phosphotransferase = no M6P tag on lysosomal enzymes =lysosomes lack enzymes = accumulations in lysosomes
I-cell Disease (Mucolipidosis II) inheritance pattern and symptoms
- AR
- Alpha/beta
- Bone deformities, kyphosis, clubfeet, contractures, dystosis complex
All LSD’s except which 3 are autosomal recessive?
Fabry disease, Hunter’s disease (MPS II), and Dannon disease are all X-linked
Three main categories of LSD’s
Mucopolysaccharidoses, Mucolipidoses, Sphingolipidoses
Give 6 examples of mucopolysaccharidoses
Hunter syndrome Hurler syndrome Sanfilippo syndrome Morquio syndrome Maroteaux-Lamy syndrome Sly syndrome
Give an example of each type of mucolipidoses (3)
I: sialidosis
II: I-cell disease
III: Pseudo-Hurler polydystrophy
Give 6 examples of sphingolipidoses
Gaucher's disease Niemann-Pick disease Tay Sach's disease Metachromatic leukodystrophy Krabbe disease Fabry's disease
Disease resulting from an accumulation of glucocerebrosides
Gaucher’s disease
Disease resulting from an accumulation of sphingomyelin and cholesterol
Niemann-Pick disease
Disease resulting from mutation in hexoaminidase A => Gm2 gangliosidosis
Tay Sach’s disease
Disease resulting from an accumulation of sulfatides d/t deficiency of arylsulphatase A (ARSA)
Metachromatic leukodystrophy
Disease resulting from an accumulation of galactocerebrosides
Krabbe disease
Disease resulting from an accumulation of globosides. Alpha-galactosidase A => ceramide trihexoses
Fabry disease
Symptoms of this disease are ataxia and dementia d/t destruction of myelin
Metachromatic leukodystrophy
Type of LSD that involves defective degredation of GAG’s/ accumulation of sulfated polysaccharides
Mucopolysaccharidosis
Maturation of early endosomes containing endocytic vesicles to late endosomes occurs via:
Multivesicular bodies
____ in membrane pumps H+ into lysosome, maintaining acidic pH
V-type ATPase
Where does packaging of lysosomal enzymes into vesicles occur?
The golgi network
MP6 Tag put on in cis-Golgi by:
GlcNAc phosphotransferase
To be formed, lysosomal membranes are coated by:
clathrin
If lysosome can’t degrade material within it, it becomes a ____, and either expels material from the cell or it remains as ____.
Residual body, lipofuscin
The most severe MPS, involves physical and mental deterioration from 2-4y.o., hepatosplenomegaly, skeletal deformity, coarse facial features, and corneal clouding. Death <10yrs.
Hurler Syndrome
MPS syndrome similar to Hurler syndrome but X-linked, milder, and without corneal clouding
Hunter Syndrome
Peripheral neuropathy Heart disease Renal disease Alpha-galactosidase A: Ceramide Trihexosides X-linked
Fabry Disease
Peripheral neuropathy Developmental delay Optic atrophy Globoid cells Galactocerebrosidase: Galactocerebrosides
Krabbe Disease
Hepatosplenomegaly Neurodegeneration Foam cells Zebra bodies in lipid-laden cells Sphingomyelinase: sphingomyelin Cherry red macula
Niemann-Pick
Ataxia and Dementia
Demyelination
Alrylsulfatase A: Sulfatides
Metachromatic Leukodystrophy
Neurodegeneration
Cherry red macula
Onion skinning of lysosomes
Hexosaminidase A: GM2 gangliosides
Tay Sachs Disease
Hepatosplenomegaly
Bone issues
Tissue paper cytoplasm
Glucocerebrosidase: Glucocerebrosides
Gaucher Disease
Rare AR disorder
Delayed fusion of phagosome with lysosome in leucocytes
Autophagocytosis of melanosomes in melanocytes → albinism
Granular defects in NK cells & platelets
Chédiak-Higashi syndrome
USMLE = defect in microtubule polymerization
Name for receptors in peroxisome membrane that import cytosolic proteins
peroxins
C terminal SKL (Ser-Lys-Leu) import signal (PTS1 signal)
Peroxisome import signal
Peroxisome import signal
C terminal SKL (Ser-Lys-Leu) import signal (PTS1 signal)
2 peroxisomal reactions
Oxidases use O2 to remove H atoms from organic substrates
Catalases use H2O2 to oxidise toxins
80-90% of myelin membrane phospholipids made of this ether bonded molecule
plasmalogen
Xanthine oxidase degrades purines to ____
Uric acid
VLCFA’s can only be degraded where?
Peroxisome
PEX mutations = Defective peroxisomal biogenesis (peroxins don’t recognize SKL/PTS signals) in a spectrum of disorders called:
Zellweger spectrum- leads to peroxisome deficiency
Defective membrane protein that imports VLCFAs causes accumulation in glial cells leading to myelin breakdown and adrenal cortex leading to atrophy in a disease called:
X-linked Adrenoleukodystrophy (XALD)
Method to detect/analyze RNA
Northern blot (pride with cDNA)
Method to detect/analyze protein
Western blot
Method to detect/analyze DNA
Southern blot
Type of analysis used in criminal forensics
Restriction Fragment Length Polymorphism (RFLP)
A process that exploits the re-annealing properties of DNA and depends on complimentary base pairing
Molecular Hybridization
Enzymes that cut at specific 4-8 bp palindromes, it’s site sequencing is useful in analyzing DNA and verifying mutations
Restriction enzymes
Southern blot digests DNA using what type of enzyme?
Restriction
The probe for a Western blot analysis is:
Anti-target monoclonal antibody
_____’s use multiple immobilized simple targets and very complex probes to analyze DNA, allowing unlimited parallel assays
Microarrays
_____ arrays are replacing Northern blot
Expression
_____ arrays are replacing Southern blot
Genomic
A very large constructed plasmid used to carry big pieces of DNA into bacteria when cloning
Bacteria Artificial Chromosome (BAC)
In cloning genomic DNA, we learn nothing about _____ of gene product.
Expression
A ____ library is made from isolating mRNA and synthesizing a dscDNA. It is easier and faster to study gene _____.
cDNA, expression
A library of DNA that represents the entire genome of an organism
Genomic library
A library of cDNA molecules which represents all mRNAs expressed in a particular cell or tissue
cDNA library
A library of cDNAs cloned into expression vectors (modified plasmid or virus) that also represents all mRNAs but also allows encoded proteins to be made in eukaryotic host
Protein Expression Library
A tissue specific assay in which limited digestion by DNase marks regions in chromosomes that lack nucleosomes and thus can bind TFs, reflecting cell-specific gene expression
DNAse Hypersensitivity Assay
What genes typically encode enzymes which have sensitive assays or unique activities?
Reporter genes
What is a commonly used reporter gene in mammalian systems?
Luciferase (glow)
What gene modification is useful for studying normal/mutant gene interactions?
Gene knock-in
What gene modification is useful for studying the effect of point mutations?
Gene replacement
What gene modification is useful for studying gene deletions?
Gene knockout
A process that adds a 28bp artificial ds microRNA to the cell which is modified by dicer and loaded to RISC, capitalizing on the cells native microRNA mechanism to silence a target sequence
RNAi (interference)
Viral vector gene therapies deliver factors to produce:
IPS cells (induced, pluripotent stem cells)
A gene therapy for severe combined immunodeficiency, ______ involves removing and reintroducing cells
Ex vivo stimulation of immune system
In _____ therapy, a patient’s T cells are re-engineered using a chimeric ab receptor to be very specific
CAR T-cell Immunotherapy
What is the main catalytic component of the RISC complex?
Argonaut
_____ allows specific gene editing by homologous recombination by substituting a sequence of interest for the original RNA guide.
CRISPR/Cas9
Gene editing alternative that involves fusion of a transcription activator-like DNA binding domain with a restriction endonuease (usually Fok1)
TALEN
Two alternatives to CRISPR/cas9 gene editing
TALEN and ZFN
Gene editing mechanism that seems to be more programmable, specific, and efficient
BuD/Fok1
Two physical methods for DNA transfer into stem cells or eggs
Modified liposomes, electroporation
Yamanaka factors
Four genes carried on a retrovirus that can reprogram skin cells to become iPSCs
____ complexes actively reposition nucleosomes
Chromatin remodeling
Sequences like enhancers, silencers, and insulators are on the same DNA as the gene being transcribed and so are considered:
Cis-acting
What kind of mapping identifies regulatory boxes that control a gene?
Deletion and mutation mapping
Gene activation by steroid (4 steps)
- Diffusion
- Binding of hormone receptor protein in cytoplasm
- Receptor dimerizes and translocates into nucleus
- Binds to promoter (hormone response) element - acts like TF, recruits co-activator/repressor to begin chromatin remodeling
Point mutations in the zinc finger TF GATA4 result in what malformation that results in 50% of what surgery in the US?
Bicuspid aortic valve, valve replacement
Mutations in HOXD13 TF result in what malformation?
Synpolydactyly
Mutations in Runx2 result in an AD haploinsufficiency disease called:
Cleidocranial dysplasia
Mutations in Lmx1b TF result in AD dorso-ventral patterning of limbs called:
Nail Patella Syndrome
Globin synthesis in reticulocytes is regulated by (unstable) phosphorylation of:
eIF2
~50% of protein encoding genes lack a TATA box and have CpG islands, they are called:
Housekeeping genes
An AD type of hemolytic anemia in which there is an erythrocyte spectrin deficiency, RBCs are spheroidal, and splenectomy can improve symptoms is:
Hereditary spherocytosis
What is the default pathway for secretion which is followed by vesicles destined for the apical or basolateral plasma membrane?
Constitutive secretion
Vesicles with a signal that are destined for the plasma membrane follow ____ secretion pathways
Regulated
In transcytosis, which involves both endo- and exocytosis, what determines the direction of vesicles movement?
pH
The coat type that travels from ER to GN is:
COPII
The coat type that is involved with endocytosis is:
Caveolae
The coat type involved with transport from TGN to the ER is:
COPI
The coat type involved in ER and plasma membrane traffic is:
Clathrin
KDEL and KXXX are tags for:
ER
What protein is involved with vesicle docking?
Rab-GTP
What 2 G-proteins are recruited by GEF to help with vesicle formation?
When they and the COP coat disassemble, what is exposed?
ARF/SAR-GTP, v-SNARE
After the vesicle is docked, what proteins help with fusion? What proteins release the complex after fusion?
V and T SNARES, NSF/SNAPS
In what disease is ACETYLCHOLINE release inhibited due to cleavage of v-SNARES by a toxin?
What symptom results?
Botulism, flaccid paralysis
In what disease is GABA/GLYCINE release inhibited due to cleavage of v-SNARES by a toxin?
What symptom results?
Tetanus, spastic paralysis
What disease results from a deficiency of alpha-L-iduronidase resulting in accumulation of dermatology sulfate and heparin sulfate?
Hurler Syndrome (MPS 1)
In the cis golgi, oligosaccharide modification is ____ linked and glycosylation is ____ linked
N, O
M6P tag is added in the ___ golgi
Cis
Sulfate is added in what part of the golgi?
Trans
What cell membrane component is flipped from the inner to outer leaflet to signal apoptosis?
Phosphatidylserine
Adrenergic and olfactory receptors are:
G-Protein Coupled Receptors
GFR’s and Insulin use what type of receptors?
Receptor Tyrosine Kinases (RTK’s)
TGF beta uses what type of receptor?
Serine/threonine Kinase Receptor
Cytokine and integrin receptors are:
Receptors without kinase activity (linked to seperate TK)
Neurotransmitter receptors are:
Ion channel-linked receptors
An example of receptor TK use would be:
GFR’s and insulin use RTK’s
An example of GPCR use would be:
Adrenergic, chemokine, rhodopsin and olfactory receptors
Ion channel-linked receptors are used for:
Neurotransmitters
Steroid hormone receptors are:
Intracellular
GPCR’s activate which two effector proteins?
PLC and adenylyl cyclase
RTK’s activate which two effector proteins?
PLC and PI3K
PLC produces what 2 second messengers?
IP3 (triggers Ca2+) and DAG
IP3 and DAG result in the activation of:
PKC
PKB is activated by:
PI3K
Activation of PKB results in cell___ and inhibition of ___
proliferation, apoptosis
cell survival
Activation of RTK reveals ___ protein docking site, which binds___ and thus activates the small Gprotein ___. This then activates ___ resulting in cell proliferation/growth.
GRB2, SOS (GEF), Ras, MAPK
The Ras-MAPK pathway involves:
RTK activation GRB2 docking site Gef/SOS binding MAPK activation GF increase
The JAK/STAT pathway is used for:
Cytokine receptors/receptors without kinase activity
Integrin receptors lack kinase activity, so use 2 other kinases:
ILK (Integrin linked kinase) and FAK (Focal Adhesion Kinase)
How does PKB inhibit apoptosis
PKB inhibits BAD,
BAD inhibits BCL-2,
BCL2 inhibits BAX,
BAX forms porins
____ carries microtubules towards the + end (anterograde)
Kinesin
____ carries material towards the - end (retrograde)
Dynesin
Which cytoskeleton fiber is the strongest and connects adjacent cells?
Intermediate filaments
Which cytoskeleton fiber if found around the inside of the cell and is responsible for support and villi?
Microfilaments (actin)
Which cytoskeleton fiber is primarily responsible for movement of organelles and vesicles?
Microtubules
What type of motor protein interacts with actin microfilaments?
Myosin
What are the subunits that make up microtubules?
13 protofilaments (columns) of alpha/beta tubulin dimers
Which tubulin subunit type contacts the - end of the filament?
Alpha
-bound to centrosome
Rapid growth/shrinkage of microtubules due to GTP hydrolysis is known as:
Dynamic instability
Microtubule _____ make up cilia and flagella
Doublets=axoneme
9 microtubule _____ make up centrioles and basal bodies (MTOCs)
Triplets
What is the scaffold for microtubule growth in the MTOCs?
Gamma-tubulin (binds alpha tubulin)
A protein that stabilizes microtubules and a famous example relates to Alzheimer’s disease
MAPs and Tau protein
Domains of mRNA processing in the nucleus, rich in splicing snRNPs
Speckles
Tangled, coiled threads, often paired, involved in snoRNA biogenesis and trafficking as well as cytoplasmic SMN and Gemin 2
Cajal bodies and gems
3 nucleolar substructures
Fibrillar center, dense fibrillar component and granular component
2 pathogenic causes of Alzheimer’s disease
Beta-amyloid plaques and neurofibrillary tangles (hyperphosphorylation of tau)
What gene is a major risk factor for earlier age of late onset Alzheimer’s?
Apo E4
What type of microtubule pulls centeosomes apart?
Kinetichore microtubules
50% or primary ciliary dyskinesia are considered:
Kartagener syndrome
Kartagener syndrome symptoms include:
Bronchiectasis
Situs inversus
Chronic paranasal sinusitis
Infertility
Colchicine, vincristine, and vinblastine are drugs which:
Bind tubulin subunits and prevent polymerization
Paclitaxel (Taxol) works by:
Binding and stabilizing microtubules, blocking mitosis in cancer cells since the mitosis spindle can’t be broken down
Epidermolysis Bullosa Simplex is an AD mutation of:
Keratin 5 or 14
What intermediate filament is expressed in muscle cells? Nuclei?
Desmin, lamin
What intermediate filament is expressed in glial cells?
GFAP
