Notch and Integrin Signalling

Question 1

what type of signalling is notch?

Answer 1

juxtacrine

Question 2

why is the notch pathway important?

Answer 2

for development and cancer and it determines cell fate specificity (i.e. makes cells different from each other)

Question 3

what are three things that notch signalling achieves for determining cell fate specificity?

Answer 3

lateral inhibition
lineage decisions
establishing boundaries

Question 4

what is the basic concept of notch signalling?

Answer 4

transmembrane ligand binds transmembrane receptor
the receptor is notch
the ligands are delta, serate/jagges
there is a DSL domain

Question 5

what three components does the DSL complex consist of?

Answer 5

delta
serrate
lag-2

Question 6

what are the two proteolytic cleavages that come from ligand binding in notch receptor?

Answer 6

extracellular (adam-family metalloprotease)

within transmembrane domain (y-secretase: a complex)

Question 7

what components are within the y-secretase complex?

Answer 7

presenilin, nicastrin, PEN2, APH2

Question 8

what occurs in the nucleus during notch signalling?

Answer 8

Nicd activates target gene expression by interacting with CSL and mastermind (mam)

Question 9

describe the notch process in the receiving cell?

Answer 9

glycosylation by o-fucosyl transferase (chaperones notch to membrane)
glycosolation by fringe for S1 cleavage
two e3 ligases for ubiquitination of delta x and nedd4
escrt complex for the MVB

Question 10

what happens in the sending cell for notch signaling?

Answer 10

ubiquitination of e3 logase
s2 and s3 cleavages of ligand
transendocytosis of receptor to generate pulling force
ligand binding leads to proteolytic cleavages in notch receptor

Question 11

what is lateral inhibition?

Answer 11

an important function of notch pathway

makes two cells different from one another

Question 12

what is an example of lateral inhibition?

Answer 12

neuronal and epithelial cells

receving a delta signal represses the proneural genes and instead promotes epidermal fate

Question 13

what are the mechansims of lateral inhibition?

Answer 13

both cells signalling to one another
both cells have notch and delta, this is a feedback loop
there are fluctuations leading to one cell receiving more signal than the other
the receiving cell will become epidermal
feedback cements this

Question 14

what are focal adhesions in integrn signalling?

Answer 14

integrin heterodimers bind to ecm

adaptor proteins link focal adhesion to actin cytoskeleton usign scaffold proteins

Question 15

what are the three types of molecules associated and located in the ECM?

Answer 15

proteoglycand and glycosaminoglycans
fibrous proteins
glycoproteins

Question 16

what is the basal lamina?

Answer 16

specialised ECM secreted by epithelial cells

Question 17

what are the roles of the basal lamina?

Answer 17

structure
cell polarity
promoting cell sirvival, proliferation, differentiation
cell migration

Question 18

what are the major components of the basal lamina?

Answer 18

laminin and type 4 collagen

Question 19

what is laminin?

Answer 19

a heterodimer that interacts with nodogen etc and is the primary organiser of the basal lamina

Question 20

what are integrins?

Answer 20

heterodimers made of alpha and beta subunits
interact with cytoskeleton to interact with ECM
have active and inactive conformations

Question 21

what are 5 downstream components of integrins?

Answer 21

talin
integrin linked kinase
focal adhesion kinase
vinculin
paxilin
alpha actinin

Question 22

what is inside-out signalling?

Answer 22

activation of integrins via talin
talin is recruited to membrane and there are secondary messengers and small gtpases
leads to focal adhesion

Question 23

what is outside-in signalling?

Answer 23

proliferation
cell cycle
cytoskeleton and polarity