Cell-Matrix interactions

Question 1

Transmembrane Proteoglycans

Answer 1

Syndecan binds fibronectin and coll (fibrillar 1,3,5). Assists Cell adhesion to ECM

Question 2

Adhesive Glycoproteins: ECM-Cell

Answer 2

Laminin (BL) and fibronectin (cell matrix) bind to integrins via RGD sequence

Question 3

Integrins info

Answer 3

alpha/beta heterodimers
primary cell receptor for binding ECM (coll, fibrin, laminin) use velcro principle (increased number of weak interactions allowing migration and movement)
Also function in cell-cell adhesion molecules in leukocytes and platlets

Question 4

Integrins and intracell signaling

Answer 4

1. Adhesion dependent activation of cytosolic signal proteins regulate anchorage dependent growth
2. Growth factor dependent cascades reversing integrin clustering, decreasing adhesion therefore increasing cell motility

Question 5

Anchoring junctions formed by Integrins

Answer 5

1. Focal adhesions: Integrins bind to actin stress fibers via adapter protein and to fibronectin (weak)
2. Hemidesmosomes: Integrin bind to IF (keratins) via adapter proteins and to laminin (strong)

Question 6

Focal Adhesion path

Answer 6

1. Integrin binding to ligand in ECM - cytoplasmic tail binds anchor proteins - Vinvulin and Talin (adapters for integrin and actin) or alpha actin (cross link actin stress fibers)
2. Actin binding results in clustering of integrins and tighter binding to ECM proteins - forms focal adhesions

Question 7

Focal Adhesion function

Answer 7

1. Focal adhesions used as feet in migrating cells = motility
2. Integrins signal through focal adhesion kinase (FAK), regulating RhoGTPases (prolif, survival, migration) = MAPK and PI3K pathway

Question 8

Hemidesmosomes

Answer 8

Strongest anchor btwn cell and ECM: basal surface epithelial cell and BM = nonmotile
Intracell IF (keratin) are embedded into plaques = plectin
Integrins (alpha6beta4) link intracell plaques to ECM laminin
Anchored by coll 7 fibers in eCM (anchor dermal-epi dermal jx; BL to CT)

Question 9

Cell migration

Answer 9

Often irt external signals (chemotaxis) - initial cell proliferation
Important for embryogenesis, tissue repair, infection control
Reorg of cell architecture
Main motor = leading front (active polymer)

Question 10

G proteins in cell motility

Answer 10

Rho family = RACm CDC4, Rho

Question 11

G proteins location in cell motility

Answer 11

1. Lamellipodia (RAC): leading edge of moving fibroblasts, extended with broad flattened fluffy projection
2. Filopodia (CDC4): thin spike like protrusions at leading edge of moving cell (“sensors”)
3. RAC - rearranges actin to stretch front out in lamellopodia: old focal pt released -> Rho mediated new focal contacts made

Question 12

Small G proteins regulating Actin Cytoskeleton

Answer 12

1. Fibroblasts - cortical actin filaments few focal contacts
2. Rho - stress fibers and focal contacts
3. Rac - lamellopodia extends from entire circumfrence of cell
4. CDC4 - filopodia protrusions form adhesive contacts with substratum

Question 13

Cell migration and invasion

Answer 13

Matrix Metelloproteinases (MMPs)=collagenases
Proteinase inhibitors (TIMPs)
Stored in ECM, release and activated under tight control. Allows tissue remodel and selective cell migration (implantation, repair, immune response)
Uncontrolled digestion of ECM occurs in tumor invasion

Question 14

Bullous Pemphigoid

Answer 14

Autoimmune blistering disease, auto antibodies to hemides protein. Disrupts dermal-epidermal junction, subepidermal blisters or psorisiform pattern.
Present >60yrs, Itchy