1. Cell and Molecular Biology
Gerald Karp
Cell and Molecular Biology
Fifth Edition
CHAPTER 7 Part 1
Interactions Between Cells
and Their Environment
Copyright © 2008 by John Wiley & Sons, Inc.

2. 7.1 The extracellular space
Glycocalyx (cell coat): cell-cell interaction cell-substratum interaction

3. The extracellular matrix (ECM)
plays a regulatory role in determining the shape and activities of cells
a. Collagen
b. Proteoglycans
c. Fibronectin
d. laminin

4. Best-defined ECM
Basement membrane (basal lamina): a continuous sheet nm thick that
(1) surrounds muscle and fat cells
(2) underlies the basal surface of epithelial tissues or the lining of the digestive and respiratory tracts
(3) underlies the inner ECs of blood vessels

5. a. Collagen (fibrous glycoprotein)
Found throughout in animal kingdom
High tensile strength, that is, their resistance to pulling forces is strong
A collagen fiber 1 mm in diameter is capable of suspending a weight of 10 kg without breaking.
Is the single most abundant protein in human body (25%)

6. Collagen (Cont.)
Is produced primarily by fibroblasts, smooth muscle cells and epithelial cells
More than 20 distinct types of collagen have been identified
All share at least two structural features: trimers of α chains and wound around each other to form a rod-like triple helix

7. Tendons : connect muscle and bone
Stroma of cornea: transparency
Type I collagen gene mutation: thin skin, death
Type II mutation (cartilage tissue): skeletal deformaties
Other mutations: hyperflexible joints, highly extensible skin

8. b. Proteoglycans (protein-polysaccharides complex)

9. The GAG chains also act as binding sites for many growth factors, affecting their interaction with cell-surface receptors
GAG “-” H3O ”+”
Hydrated gel with pores resists crushing forces
Collagens and GAGs give cartilage and other ECM strength and resistance to deformation.

10. c. Fibronectin

11. d. Laminin Three different polypeptide chains connected by S-S bonds
Long arm and short arm
Effect on cell migration and cell differentiation (laminin receptor on cell surface) i.e. guiding tips of embryoic axons, migration of primordial germ cell

12. Matrix metalloproteinases (MMPs)
Zinc containing proteins either secreted into the extracellular space or anchored to the plasma membrane
Tissue remodeling
Migration
Wound healing
Angiogenesis

13. Athritis
Atherosclerosis
Hepatitis
Tooth and gum diseases
Tumor progression

14. 7.2 Interactions of cells with extracellular materials
Integrins (membrane receptors)
Focal adhesions and hemidesmosomes: anchor cells to their substratum
αβ chain spans membrane, non-covalently linked, 17α,8β, 20+ kinds of integrins (Fig. 7.5)

15. Integrin (cont.) Large extracellular portion Small cytoplasmic portion
Ca2+ binding site on αchain
βchain can recognize RGD sequence on fibronectin, activate FAK pathway

16. Change in conformation of the cytoplasmic domains, increasing the integrin’s affinity for an extracellular ligand
“Inside-out” theory
The aggregation of platelets during blood clotting occur only after the cytoplasmic activation of αIIbβ3 integrins which increases their affinity for fibrinogen

17. “Outside-in” signaling
Integrin binds to fibronectin or collagen
Conformational changes at the cytoplasmic end of the integrin
FAK
Protein phosphorylation
Nucleus (cell division, differentiation, motility, growth, survival, cancer cells vs. normal cells)

18. Integrins link ECM to cytoskeletons
Focal adhesion (in vitro with actin)
Hemidesmosomes (in vivo with keratin, IF)
Out-side-in
Normal cells (integrin dependent) and malignant cells (integrin independent)

19. Bullous pemphigoid
Individual’s bp proteins (autoantibodies) present in these adhesive structures.
These autoantibodies cause the lower layer of the epidermis to lose attachment to the underlying basement membrane.
The leakage of fluid into the space beneath the epidermis results in severe blistering of the skin.
Epidermis, GI, urinary tracts

20. 7.3 interactions of cells with other cells
Cells can recognize the surfaces of other cells
Interacting with some and ignoring others

21. Little was known about the nature of the molecules that mediate cell-cell adhesion until
The development of techniques for purifying integral membrane proteins
The isolation and cloning of genes that encode these proteins

22. Four distinct families of integral membrane proteins play a major role in mediating cell-cell adhesion
Cell-cell adhesion molecules
1. Selectins
2. Certain members of IgSFs and
integrins
3. Cadherins
4. Adherenes junctions and desmosomes:
anchoring cells to other cells

23. 1. Selectins LEU-CAM1 (L-selctins) in vivo: lymphocytes homing
A family of intergral membrane glycoprotein
Bind to the oligosaccharides of other cells
Possess a small cytoplasmic domain and a large extracellular segment
Role of selectins in inflammation (P.263)

24. 2. Immunoglobulins and integrins
Ig domains: amino acids
Most IgSF mediate lymphocytes and macrophages and target cells for immune response
Calcium-independent cell-cell adhesion
Some IgSF such as VCAM, NCAM and L1 mediate interaction between nonimmune cells i.e. nerve outgrowth, synapse formation, nervous development
Deformed babies due to L1 mutation, water on the brain, mental retardation
Integrins α4β1 binds to VCAM on blood vessels

25. 3. Cadherins Transmit signals from ECM to the cytoplasm
Mediate Ca2+-dependent cell-cell adhesion
E-cadherins, N-cadherins, P-cadherins

26. 4. Adherins junctions and desmosomes: anchoring cells to other cells
Adhesive junctions (ca2+dependent):
1.adherens junctions
2.desmosomes
3.junctional complexes (tight junction and gap junction)