Beyond the Cell II

1
Beyond the Cell II

• Reading Becker, ch. 11

2
Proteoglycans at Interface of Cell and Matrix

• Proteoglycans can serve as points of contact
  between cell and ECM
• Part of protein core may be an integral membrane
  protein
• Can be covalently attached to phospholipids in
  the membrane
• Can be bound to specific receptors lying within
  the membrane

3
Adhesive Glycoproteins

• Considered part of the matrix
• Link the matrix to the cell
• Bind to proteogylcans and/or collagen in the ECM
  as well as to membrane receptors in the cell

4
2 Most Common Adhesive Glycoproteins

• Fibronectins
• Laminins

5
Fibronectins

• Multiple isoforms of fibronectin arise from a
  single fibronectin gene via alternative splicing

6
Fibronectin Structure

• Dimer of 2 fibronectin monomers linked by 2
  disulfide bonds
• Globular domains have distinct functions
• Cell-surface binding domain contains RGD sequence
  recognized by cell surface receptors

7
Migratory Cells Follow a Path of Fibronectin
8
Fibronectin and Blood-Clotting

• Plasma fibronectins forms found in the
  bloodstream
• Interact with blood platelets and fibrin
• Fibrin a blood clotting protein
• Interaction of fibronectin with fibrin occurs via
  the fibrin binding domain

9
Laminins and the Basal Lamina

• Laminins are 2nd major group of adhesive
  glycoproteins in the ECM
• Present in basal laminae
• Basal laminae thin sheets of matrix that form
  barriers between epithelial cell layer and
  underlying connective tissue
• Also form around certain cell types, such as
  muscle cells, fat cells, Schwann cells

10
Laminin Structure

• 3 polypeptide chains (a, b, and g)
• Have globular domains with distinct functions
• a chain can bind to cell surface receptors
• All 3 chains can bind to ECM components
• Function anchor epithelial cells to the basal
  lamina

11
Integrins

• Large family
• TM glycoproteins
• Bind to adhesive glycoproteins in ECM
• Linked to the cytoskeleton intracellularly

12
Integrin Structure

• Dimer of 2 TM subunits (a and b)
• Many different as many different bs
• Many different combos of ab dimers
• Combo determines specificity of integrin for
  adhesive glycoproteins outside
• a5b1 binds fibronectin
• a6b1 binds laminin

13
Integrins are Linked to the Cytoskeleton
Intracellularly

• Focal adhesions
• EC domain of integrin (a5b1) binds
• to fibronectin in ECM
• IC domain of integrin binds to talin
• Talin binds to vinculin
• Talin and vinculin are linker
• proteins
• Vinculin binds to actin

Migratory Fibroblast
14
Integrins are Linked to the Cytoskeleton
Intracellularly

• Hemidesmosome
• EC domain of integrin (a6b4)
• binds to laminin in basal
• lamina
• IC domain of integrin binds to
• plectin (a linker)
• Plectin binds to keratin (IFs of
• the cytoskeleton)

Epithelial Cell