lec 18- cellular adhesion

Question 1

cells in a multicellular organism must be able to bind to other cells and to the ECM, adhesion molecules are used to do this, what are the 5 categories of adhesion molecules?

Answer 1

1. immunoglobulin cell adhesion molecules (ICAMs)
2. cadherins
3. integrins
4. selectins
5. mucins

Question 2

how many ICAMs are there?

Answer 2

hundreds of them

Question 3

what are ICAMs?

Answer 3

receptors that bind to ligands on the surfaces of other cells

Question 4

what are the two ways ICAMs can bind?

Answer 4

-homotypically (to identical proteins on neughbouring cells)
-heterotypically (to different proteins on neighbouring cells)

Question 5

does the difference in binding abilities of an ICAM specify interactions of a developing mature animal?

Answer 5

yes

Question 6

what are CD?

Answer 6

CD = clusters of differentiation, surface genes recognized by monoclonal antibodies (without knowledge of the antigen)

Question 7

do immunoglobulin have 1-7 extracellular immunoglobulin domains? what do they do?

Answer 7

yes, dock into the plasma membrane using a single transmembrane helix

Question 8

are most Immunoglobulin domains a single peptide? are the C-terminal cytoplasmic tails variable in sequence and in their ability to bind to different intracellular ligands?

Answer 8

yes for both

Question 9

when does the cellular expression of ICAMs change? what does this add to?

Answer 9

it changes during development, which adds to the cellular adhesion specificity needed to generate organs

Question 10

how many members of cadherins are there?

Answer 10

more than 80 members

Question 11

is cadherin a calcium dependent like-protein binder on neighbouring cells?

Answer 11

yes

Question 12

can cadherin also do heteotypic bindng?

Answer 12

yes, even though mostly homotypic

Question 13

what is the similar domain amongst cadherins?

Answer 13

the CAD domain

Question 14

what does the CAD domain consist of?

Answer 14

110 residues arranged into a sandwich of 7 B-strands

Question 15

how do cadherins interact? how do they form trans and cis interactions?

Answer 15

-interact head-tail through their N-terminal CAD domains
-form strong (trans) interactions with neighbouring cells
-form cis-interactions with neighbouring cadherins binding in the same cell

Question 16

what adaptor proteins link cadherins to actin or IF?

Answer 16

catenins

Question 17

what do cadherins do?

Answer 17

cause contact inhibition

Question 18

explain how cadherins cause contact inhibition?

Answer 18

-when cells grow in culture they continue to move and divide until stopped through signaling brought about primarily by cadherins
-cahderin attachment sends signals through the cell that causes the exclusion of transcription factors from the nucleus to block cellular proliferation
-cell movement is blocked by impeding the functions of small GTPases

Question 19

what are integrins?

Answer 19

the main receptors for ECM adhesion

Question 20

what do integrin bind to?

Answer 20

ECM proteins (fibronectin, collagen, laminin)

Question 21

what is the structure of integrins?

Answer 21

-2 chains which are:
a-chain (18 in mammals) and B-chain (8 in mammals) which form 24 different types of dimers
-contribute to ligand binding specificity

Question 22

how is the ligand binding domain of integrin formed? when no ligand is bound, what happens to the domain

Answer 22

-its formed from 2 globular heads linked to 16 nm legs and single transmembrane regions
-the legs close in on themselves and globular heads turn towards the membrane

Question 23

can integrin have more than 1 extracellular binding partner?

Answer 23

yes

Question 24

how many integrins can different ECM proteins bind?

Answer 24

-more than one
-fibronectin binds to 9 integrin
-laminin binds to at least 5 integrins

Question 25

is the binding of ECM proteins to integrin weak to allow for adjustable grip?

Answer 25

yes

Question 26

do integrins associate with many signaling and structural proteins at structures like focal adhesions?

Answer 26

yes

Question 27

what protein is in snake venoms?

Answer 27

disintegrin

Question 28

what do disintegrins compete with?

Answer 28

fibrinogen

Question 29

what is fibrinogen?

Answer 29

a circulating protein in blood that is cleaved to make fimbrin (used for blood clots)

Question 30

what is fimbrin?

Answer 30

an ECM protein

Question 31

what do snake venoms compete with?

Answer 31

fimbrin, fibronectin, and other ECM proteins for integrin binding sites on many cells including platelets, they block integrin cell adhesion

Question 32

what primarily uses selectins?

Answer 32

white blood cells and platelets as well as other cells

Question 33

what are the 3 types of selectins?

Answer 33

E (endothelial), L (lymphocytes), and P (platelets)

Question 34

what do selectins do?

Answer 34

they are used to grab circulating white blood cells to allow them to roll, slow down, and exit the blood stream to enter tissues

Question 35

what domain do all selectins have?

Answer 35

a calcium dependent lectin domain at the very end of the protein (thought of as receptors)

Question 36

what does the calcium dependent lectin domain bind to?

Answer 36

-it binds to sugars (oligosaccharides and fucose)

Question 37

what are ligands for selectins?

Answer 37

-mucus-like glycoproteins on endothelial cells and on white blood cells

Question 38

do selectins bind to ligands with weak affinity to allow the bind to release to slow down the cell?

Answer 38

yes

Question 39

when selectins are bound, do they have a high tensile strength?

Answer 39

yes

Question 40

are selectins selective to which oligosaccharides they bind to?

Answer 40

no

Question 41

what are mucins? where are they found? what do they interact with?

Answer 41

-high negatively charged proteins -extend up to 50nm from the cell surface -found on endothelial cells, white blood cells, the surface of the respiratory tract, and gastrointestinal tract -interact with selectins