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Thanh Cell Physiology Unit III > Extracellular matrix: Last one!! > Flashcards

Extracellular matrix: Last one!! Flashcards

1
Q

2 main functions of ECM

A
  1. Scaffold for cells

2. Regulating cell functions (survival, differentiation, migration, proliferation, shape)

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2
Q

Who secretes ECM macromolecules?

A

Fibroblasts and their friends (chondroblasts, osteoblasts)

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3
Q

4 major classes of ECM molecules

A
  1. Glycosaminoglycans (GAGs)
  2. Fibrous proteins: collagen and elastin
  3. Multidomain adapter proteins: fibronectin and laminin
  4. water and many solutes
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4
Q

How are proteoglycans formed?

Structure?

A

GAGs covalently linked to proteins. High molecular weight.

“Core protein” has tetrasaccharides attached to serines for the primer for polysaccharide assembly

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5
Q

GAG - structure & function

A

Structure: large, unbranched disaccharide polymer. Contain an AA sugar (usually sulfated) and a sugar group substituted with a carboxy group (acidic sugar). NEGATIVELY charged

Function: due to neg charge and solubility, they can aggregate together and fill large volumes by forming gels.

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6
Q

Common GAGs

A 
hyaluronan, 
chondroitin sulfate, 
dermatan sulfate, 
heparan sulfate, 
keratan sulfate
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7
Q

Fibrous proteins (2 types) - structure & function

A

Collagen:

  • Most abundant proteins in mammals (25%)
  • 25 subunits forming 20 different collagens
  • Collagen I most abundant - connective tissue
  • Collagen IV - basal lamina
  • Provide tensile strength in connective tissue

Elastin:
- Elastic protein found in many tissues, forms networks

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8
Q

Multidomain adapter proteins (2 main types) - structure and function

A

General: Act as binding sites for other matrix macromolecules

Fibronectin:

  • 2 large subunits linked by S-S bond
  • subunits have functionally distinct binding domains
  • Type III fibronectin repeat binds integrins & contains Arg-Gly-Asp sequence
  • highly insoluble fibronectin fibrils

Laminin:

  • 3 subunits (a,b,g) form asymmetric S-S cross shape
  • Found in the basal lamina only
  • self-assemble via interactions between the ends of their arms
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9
Q

Water and solutes - function

A

Found in the “gel” between cells: allows for easy diffusion of nutrients and growth factors

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10
Q

Who breaks and remakes everything in the ECM?

A

Matrix metalloproteases (MMPs) & serine proteases

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11
Q

Quick! What are 2 types of fibrillar proteins and 2 multidomain adapter proteins

A

Fibrillar: Collagen & elastin
MAP: fibronectin & laminin

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12
Q

Role of adhesion in cell function and survival in metazoans

A

Adhere to each other to survive and form distinct compartments in cell.

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13
Q

3 types of CAMs and their ligands:

A
  1. Cadherins - homophilic binding with other cadherins
  2. Ig - Ig domains of Ig proteins on other surfaces
  3. Integrins - laminin, fibronectin, collagen
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14
Q

Cadherins

A

Cadherins:

  • single-pass transmembrane glycoproteins
  • found as homodimers
  • extracellular domain has 5 repeats and is Ca++ dependent
  • homophilic binding in a zipper-like fashion.

(Type of CAM)

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15
Q

Immunoglobulins (Igs)

A

IgSFs:

  • single-pass transmembrane glycoproteins
  • Homophilic binding mechanism
  • Found as monomers - do not require Ca++
  • Usually contain fibronectin type III domains close to membrane

(Type of CAM)

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16
Q

Integrins

A

Integrins:

  • Heterodimers (alpha and beta subunits)
  • Heterophilic binding
  • Lots of mix-n-match for binding selectivity
  • ECM-binding domain at end: binds laminin, fibronecti, collagen, etc
  • can attach intracellularly on the tail: attach to catenins

(Type of CAM)

17
Q

Role of CAM in signaling

A
  1. Extracellular portions of CAM interact with signal proteins to tell the cell what it’s attached to (outside-in)
  2. Cell can interact with CAM to chang eor get rid of its extracellular adhesion (inside-out)
18
Q

What are the 3 MMPs that the jerk wants us to know? Why are they important?

A

MMP2
MMP9
MMP14

They are very specific for collagen 4 in basement membrane (BM)

-Key for cancer cell to extrapolate from primary tumor and breach BM (made of collagen 4)
2, 9 , 14 are the only MMPs that can digest it.

19
Q

Example of ECM in disease

A
  1. Collagen 1 - skeletal dysplasias
  2. Fibronectin null - embryonic lethal mice
  3. laminin - nephrotic syndrome, NMJ issues
  4. MMP 2 or 13 loss - osteolysis and bone dysplasias
  5. Overexpression of MMP2, 9, 14 - high invasive cancer
20
Q

Cell adhesion in disease

A
  1. Type I leukocyte adhesion deficit - affects a particular integrin
  2. Type II leukocyte adhesion deficit - affects a selectin, a CAM involved in leukocyte rolling
  3. Cancer - early sign of carcinogenesis is change in CAM; cadherin down regulation; anchorage independence from loss of adhesion; catenins act as tumor suppressors and so their loss leads to cancer

Thanh Cell Physiology Unit III (26 decks)

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