extracellular matrix and cell adhesion

Question 1

CAMs

Answer 1

transmembrane proteins which attach extracellularly to other CAMs or multidomain proteins and intracellularly to signaling molecules inside the cell (information can flow both ways).

Question 2

Types of fibrous proteins:

Answer 2

collagen, elastin

Question 3

Types of multidomain proteins:

Answer 3

fibronectin (found all over), laminin (found in basal lamina)

Question 4

Types of CAMs:

Answer 4

cadherin (attaches to other cadherins, form calcium-activated ‘zippers,’ homodimeric), immunoglobulin (attaches to other Igs, form non-calcium-activated ‘zippers’, monomeric), integrin (attaches to ECM proteins, has intracellular signaling end).

Question 5

cell adhesion

Answer 5

cells ‘stick’ to very specific types of materials, and different cells stick to different things.

a combination of mechanical adhesion and cellular communication
the cell ‘knows’ what it’s attaching to and can respond appropriately.

Question 6

ECM to form functionally distinct _____

Answer 6

compartments in the cell and to allow cells to act in concert with each other.

Question 7

4 major classes of ECM

Answer 7

1. GAG
2. Fibrous proteins
3. multidomain adaptor proteins
4. water and solutes

Question 8

Glycosaminoglycans (GAGs),

Answer 8

large, unbranched disaccharide polymers. Typically contain an amino sugar and a sugar that’s substituted with a carboxy group (acidic sugar), sometimes with a sulfhydryl group.

Question 9

GAGs are ___ charged

Answer 9

negatively

Question 10

Proteoglycans are just

Answer 10

GAGs linked to a “core protein”.

Question 11

types of fibrous protein

Answer 11

1. collagen

2. elastin

Question 12

collagen

Answer 12

most abundant (25% of total protein weight in H. sapiens); tough polymers that provide tensile strength in connective tissues.

Question 13

elastin

Answer 13

Elastin is elastic protein found in a variety of tissues.

Question 14

alpha-1-antitrypsin deficiency involves an inability to control the breakdown of ____

Answer 14

elastin by elastase

Question 15

ties of multi domain adaptor proteins

Answer 15

1. fibronectin

2. laminin

Question 16

fibronectin

Answer 16

dimeric glycoprotein linked by disulfide bonds.
Can bind a variety of proteins (collagen, heparin, each other, etc).
can also bind integrins

Question 17

laminin

Answer 17

found predominantly in basal lamina (ECM that provides the “ground” for epithelial cells).
Heterotrimeric form in the shape of a cross.
Cross-links with itself

Question 18

water and solutes

Answer 18

Predominantly found in the “gel” between cells: allows easy diffusion of nutrients and growth factors between cells.

Question 19

role of adhesion in cell function and survival

Answer 19

need to adhere together for stability and need to adhere to something in order to survive

Question 20

3 types of CAMS

Answer 20

1. cadherin
2. Ig
3. integrin

Question 21

cadherin

Answer 21

1. Single-pass transmembrane glycoproteins.
2. Found as homodimers.
3. Activated by calcium: when activated, cadherins on one surface “zip up” with cadherins
   on the other surface (homophilic binding reaction)

Question 22

Ig (immuniglobins)

Answer 22

1. Single-pass transmembrane glycoproteins as well.
2. Unlike cadherins, operate as monomers, and binding doesn’t require Ca2+.
3. However, the Ig domains on these proteins do bind to Ig domains of Ig proteins on other
   surfaces.

Question 23

Integrin

Answer 23

1. Heterodimers (alpha and beta subunits): lots of different types of integrin, both alpha and beta, so can have lots of different combinations for binding to different things.
2. Has a ECM-binding domain at its end: can bind to laminin, fibronectin, collagen, etc.
3. Notice that the intracellular “tails” of integrins attach to various things inside the cell that
   can respond to the attachment:
4. Can be attached to catenins (tumor suppressor), cytoskeleton, etc.

Question 24

role of CAMs in signaling

Answer 24

1. CAM extracellular portions can interact with signal proteins to tell the cell what it’s attached to.
   (outside-in signaling)
2. This can go the other way: the cell can interact with the CAM to change or get rid of its extracellular adhesion. (inside-out signaling)

Question 25

roteins associated intracellularly with CAMs:

Answer 25

1. Cytoskeletal proteins to anchor the CAMs in the cell membrane (mechanical linkage): often actin- binding proteins.
2. Signaling proteins: often protein kinases or GTPases.

Question 26

Signaling proteins:

Answer 26

often protein kinases or GTPases.

1. tyrosine kinases
2. src
3. protein kinase C
4. Rho GTPases.

Question 27

selectin”:

Answer 27

CAMs that “catch” leukocytes coming out of the bloodstream. Mutations in
this protein can cause obvious problems.

Question 28

ECM and cell adhesion in the context of disease processes

Answer 28

1. Cell adhesion molecules, since they often control apoptosis and proliferation, are frequent targets
   for cancers and viral oncogenes (ie v-src).
2. cell adhesion is also intimately involved with immune response (mainly integrins):
   so, problems with CAMs can lead to compromised immune function.