Module 1 Flashcards
Types of Multipotent Cells
Hematopoietic, Mesenchymal, Skin, Neural, and Epithelial
Stem cell commitment
is a stepwise process, transcription factors turn certain developmental pathways on and shut others off (this determines what cell type it will become)
Asymmetric cell division
maintains stem cell populations by creating two different daughter cells from mitosis. one daughter cell is a stem cell while the other has the ability to differentiate (due to cell polarity during cell division this daughter cell does not have any proteins that help keep the cell in stem cell form)
Induced pluripotent stem cells
aka cellular reprogramming, this is done by the overexpression of stem cell maintenance proteins in somatic (unipotent) cells
Where are stem cells found in the human body?
Umbilical cord blood, dental pulp of mandibular third molars, deciduous teeth that have been shed, and periodontal ligament cells
Stem cell niche
saves stem cells from depletion and protects the human from overproduction of stem cells. ECM interactions are known to play an important role in maintaining the niche
Glycoaminoglycans (GAG) structure
Repeating dissacharide chains of acidic sugar-acetylated sugar
Negative surface charge
covalently attach to proteins to form proteoglycans
proteoglycan aggregates –> fir tree appearance
Collagen Synthesis
- translation into RER
- vitamin C dependent hydroxylation of pro and lys residues
- some hydroxylysine residues are glycosylated
- triple helix formation
- secretion into ECM and cleavage
- formation of mature collagen
Elastin
enables skin to stretch without tearing (lungs, arteries etc)
contains little hydroxyproline and no hydroxylysine
interacts with fibrillin in ECM
form desmosine cross links
Fibrous Proteins and disease
Scurvy - vitamin C deficiency
Osteogenesis Imperfecta - abnormal collagen (type 2 lethal) or decreased collagen (type 1)
Ehlers-Danlos Syndrome - defects in collagen causing stretchy skin
Marfan Syndrome - defect of fibrillin-1 tall and thin long fingers
a1-antitrypsin deficiency - reduced ability to inhibit elastase from neutrophils in lungs which causes breakdown of lung tissue
Adhesive proteins
join ECM components to eachother and cells to the ECM
fibronectin - connective tissues
laminin - epithelial tissues
Cell adhesion molecules
Cadherins
Selectins
Immunglobulin Superfamily
Integrins
Cadherins
Ca2+ mediated cell-cell adhesion
1 cadherin binds to another in the ECM by joining actin of the cytoskeletons
major role in holding cells together and tissue integrity
Selectins
transiet cell-surface binding
connects cells by binding protein on surface of one cell to carbohydrate on the surface of another
important in the bloodstream with WBC
Immunoglobulin Superfamily
cell-cell adhesion with transient expression
important during development and regeneration
Integrins
Both cell-cell AND cell-ECM adhesion
integrins bind to fibronectin and laminin in the ECM (depends on tissue type)
multiple weak adhesions due to low binding affinity
Hetero vs euchromatin
heterochromatin = more tightly packed and less transcription euchromatin = less tightly packed and more genes are located within this region
Ribosomes
40% protein and 60% rRNA
Treacher Collins Syndrome
genetic disorder affecting ribsome biogenesis
defective treacle gene causing improper trxn of rRNA for 28S subunit
Rapid growth (RER vs SER)
during rapid growth there is a lower concentration of RER which means less proteins are being secreted outside of the cell to meet the metabolic demands inside the cell
Cystic Fibrosis
mutations in the CFTR gene that distrupt normal protein conformation and traps proteins in the ER (which normal deals with the unfolded protein response to correctly fold proteins)
Peroxisomal disorders
X-linked adrenoleukodystrophy
Zellweger syndrome
Lipids in each leaflet
Outer - SM and PC
Inner - PI, PE, PS
FRAP
shows that proteins can redistribute throughout the lipid bilayer
Lipid rafts
cholesterol enriched microdomains in the plasma membrane
functions include cholesterol transport, endocytosis, signal transduction
spectrin
actin binding protein that provides stability, strength, support for the plasma membrane
spectrin forms dimers and then tetramers with itself
Actin
regulation of physical state of cytosol (gel/sol state)
cell movement
contractile rings during cell division
G-actin monomers hydrolyze ATP to polyermize into F-actin. eventually reaches a steady state where rate of addn to the PLUS end=rate of sub to the MINUS end
Actin binding proteins
- regulators of gel/sol state
- spectrin (association requires ATP & important in RBC)
- dystrophin (in skeletal muscle cells)
intermediate filaments
do not disassemble and assemble rapidly like actin and microtubules
stable & intact structures in the cell
fibrous and provide structural support
microtubules
motility, chromosomal movements, organelle and vesicle transport
protofilaments form cylindrical structure and GTP bound heterdimers (composed of alpha and beta tubulin) add to the plus end, this is called the GTP cap
Once the GTP cap is gone, the microtubule cannot grow any longer
dynamic instability
General mechanism for all G-protein receptors
ligand binds to receptor and causes a conformational change on the cytoplasmic side of the plasma membrane which binds and activates G-protein (alpha subunit) by replacing GDP with GTP
Alpha subunit then goes on to react with an enzyme regulated by G protein –> relays the signal from the first message (ligand) to deeper into the cell by producing mediators aka second messengers
The secondary messenger activates a Ser/Thr kinase that phosphorylates proteins (amplifies signal from original primary messenger) which results in a biological response
types of receptors
- g protein receptors
- catalytic receptors
- intracellular receptors
Adenylyl cyclase
once the alpha subunit of g protein binds to adenylyl cyclase, ATP gets converted to cAMP which acts as a secondary messenger in the cell
cAMP then goes on to regulate protein kinase A (PKA)
PKA phosphorylates proteins which have biological affects in the cell
Aberrant activity of Gs and Gi proteins
Cholera - modifies alpha subunit on Gs in intestinal cells which makes it so it cannot be shut off. this results in the overpdn of cAMP and diarrhea and dehydration
Pertussis - modifies Gi in the respiratory tract so it inhibits the alpha subunit from shutting adenylyl cyclase off
Phospholipase C
regulated by G protein
2 secondary messangers produced: IP3 and DAG(anchored in the membrane)
IP3 then binds to ER to release calcium
Ca and DAG work together as secondary messengers by activating protein kinase c (PKC)
PKC phosphorylates proteins in the same way that PKA does
Catalytic receptors
3 domains: ligand binding, transmembrane, effector region (within cell)
upon binding of ligand, two receptors form dimers
each receptor tail tyrosine phophorylates the other in the dimer
SH2 (adaptor protein) then is able to bind to the phosphorylated tyrosines
Ras
homologous to the alpha subunit of G protein
Ras binds to SH2 containing domains that are already bound to the phosphorylated tyrosines
Ras activates the MAP kinase cascade (much longer lived that tyrosine phos.)
Final enzyme: MAP kinase gets phosphorylated and translocates to the nucleus to act as a trxn factor
STATs
signal transducers and activators of trxn
SH2 containing proteins that can bind directly to the phosphorylated tyrosines (unlike Ras)
STATs get tyrosine phosphorylated and form dimers –> translocate to nucleus to act as trxn factor
inhibitors of DNA synthesis
5-Fluroruracil
methotrexate
