Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
28 Cards in this Set
- Front
- Back
|
Why is cell adhesion important?
|
development, survival, and organization of tissues
|
|
|
What are integrins? (
|
-proteins located on the cell surface
-attaches cytoskeleton (inside cell) to extracellular matrix outside the cell -signal transduction from ECM to inside the cell |
|
|
What are integrins used for?
|
-cell motility
- |
|
|
Structure?
|
-transmembrane heterodimers
-binds to a matrix protein outside the cell and to the actin cytoskeleton inside the cell creating a transmembrane linker -alpha subunit is cleaved into one small transmembrane domain, and 1 large extracell domain that has 4 calcium binding sites - the 2 domains can be reduced bc held together by dsulfide bond -Beta subunit is 1 chain w/ cysteine rich region |
|
|
why cation binding sites?
|
-type of divalent cation can influence both the affinity and specificity of the binding of an integrin to its ligand
|
|
|
What are integrins used for?
|
-cell motility
-Signal transduction from the ECM to the cell -Connection with ECM molecules can cause a signal to be relayed into the cell through protein kinases that are connected with the intracellular end of the integrin molecule. -these signals promote cell growth, survival and proliferation |
|
|
How are integrins involved in adhesion and signaling events?
|
extracell talks to inside cell by lateral shifts and conf. changes that leads to clustering
|
|
|
What disease states are associated with a loss of cellular adhesion?
|
-Beta 4 mutation (JEB):blistering disease
-Beta 3 mutation in blood platelets can't bind matrix protein fibrinogen used for blood clotting so glanzmann's disease causes excess bleeding |
|
|
How are integrins activated?
|
outside in: ligand binding alters integrin conformation
inside out: signals inside cell alter integrin affinity for ligand (possible phosphorylation of cytoplasmic tails of integrin) that induces conf. chang of extracell domain (calcium shifts) |
|
|
why are there so many integrin combinations ?
|
-they are all tissue specific
- very different distributions -a variety of heterodimers can be formed from many alpha and beta subunits -beta 1 has huge phenotype |
|
|
How can integrins be turned off ?
|
degrade them
|
|
|
what integrins are associated with epethilial cancers ?
|
alpha 6 and alpha 3 laminin receptors
|
|
|
How are integrins involved in cell migration?
|
integrin is part of the focal adhesion, a little back from the leading edge, connected to actin fillaments which coordinate pushing and pulling of cytoskeleton--nucleus is included
|
|
|
what normal processes require cell migration?
|
wound healing
new vessels blood clotting immunes system remodeling colon |
|
|
what cellular components are essentail for cell migration?
|
actin fillaments, integrins, kinases, filopodia, lamellopodia
|
|
|
Give some examples of abnormal cell migration
|
metastisis, excessive bleeding
|
|
|
what are the major dependent steps in metastasis
|
1)migrate in the stroma
2)migrate along the extracellular matrix 3)intravisate, extravisate |
|
|
How are migration signals coordinated with growht signals
|
-receptor tyrosine kinases
-you won't get migration unless you have both growth factors and activated integrins working together |
|
|
when a cell migrates what components are in the leading strand
|
integrins
filopdia:contains bundles of actin lammelipodia |
|
|
How is the leading edge of the cell different from the lagging edge?
|
leading edge: electon dense (protein concentration)-interact with extracellmatrix
lagging edge: no contact |
|
|
what is Epidermolysis Bullosa?
|
-blistering caused by mutation
divided into: -(epidermal/simplex)mild trauma,hemidesmosome changes -JEB: Junctional types have blisters separateing at the lamina lucuda of the basement membrane ,includes A6B4 integrin, laminin -dermal type with blisters below basement membrane (damgage to anchoring fibrils) |
|
|
Name the genes that are mutated leading to JEB
|
-collagen fibrils
-integrins -laminins-> extracellular ligand |
|
|
what determines the severity of the disease?
|
what the position is for the defect
|
|
|
Most integrin knock-out phenotypes are lethat after birth of the mouse. Why are the B1 integrin gene mutations lethal at stage 5.5?
|
B1 forms dimers with many distinct alpha subunits, so therfore it is needed
|
|
|
JEB patients may benefit from the use of keratinocyte stem cells. What are the benefits and risks of such a strategy?
|
-might get too much adhesion
-it needs to be very directed in terms of location amount and percistence |
|
|
what disease is characterized by a defect in collagen VII
|
dystrophic/ dermal epidermolysis bullosa
-blistering below basal lamina |
|
|
what molecules are involved in autoimmune blistering disease
|
antibodies->hemidezmozomes
|
|
|
Postulate why autoimmune blistering diseases are associated with malignancy?
|
promote inflammation, chronic wound healing, disorganization of structure
|
