Cell Bio ECM (7)

  1. Types of ECM Molecules
    • Collagens
    • Proteoglycans
    • Matricellular Proteins (Adhesive Glycoproteins)
    • Integrins
    • Cadherins
    • CAMs (Cell Adhesion Molecules)
    • Elastic fibers (Elastin)
    • Matrix Metalloproteases (MMPs)
  2. Collagens
    • provide structural integrity for bone and cartilage; also major component of basement membranes
    • •Type I: fibril-forming & found almost everywhere (bONE especially)
    • •Type II: fibril-forming & almost exclusively in cartilage (car-two-lage)
    • •Type IV: network/sheet-forming type that plays a role in basement membranes (basal lamina)
    • •Type XVIII: basal lamina around blood vessels
  3. •Type I + II = connective tissue collagens
    • •Type II = cartilage collagen
    • •Type IV = epithelial basement membrane/basal lamina collagens
  4. Endostatin
    • fragment of Type XVIII (18) Collagen that inhibits angiogenesis
    • • likely anti-cancer by inducing apoptosis in endothelial cells
  5. Diseases of Collagen Defects
    • 1. Goodpasture’s Syndrome
    • 2. Alport Syndrome
    • 3. Menke’s Disease
    • 4. Ehler-Danlos Syndrome
    • 5. Scurvy
    • 6. Osteogenesis Imperfecta
    • - G A M ED S OI -
    • O(i)MG SE(d)A! OMG SEA!
  6. Goodpasture’s Syndrome
    • autoimmune disease in which antibodies to Type IV collagen destroy the basement membrane in the lungs and kidneys
    • •this is the one where you have to consider which is worse, losing kidney or lung function?
    • •treatment = corticosteroids, immunosuppressants
  7. Alport Syndrome
    •genetic disorder in which type IV collagen is absent or non-functional --> KIDNEY failure
  8. Menke’s Disease
    • X-linked recessive disease --> causes a deficiency in copper utilization --> results in faulty collagen cross-linking
    • •causes developmental delays, seizures, failure to thrive, & characteristically kinky, colorless, & easily broken hair
  9. Ehler-Danlos Syndrome
    • a connective tissue disorder --> results from a defect in collagen synthesis & assembly
    • •without the collagen to stabilize the connective tissue, tissues become more elastic (bendy fingers)
    • •has consequences in both the musculoskeletal & vascular system
  10. Scurvy
    Vitamin C deficiency prevents cross-linking of collagens; deficiency leads to spots on the skin, spongy gums, & bleeding from mucous membranes
  11. Osteogenesis Imperfecta
    • autosomal dominant disorder --> causes a mutation in Type I collagen
    • •mutated collagen in bones results in brittle bones & multiple fractures (case study where girl was taken away from her parents)
  12. Major Functions of Proteoglycans:
    • 1) Regulate hydration state of tissues, especially cartilage
    • 2) Provide resistance to impact (shock absorbers) in cartilage
    • 3) Act as reservoirs for growth factors and cytokines
    • It’s the carbs that count!
  13. Chondrodysplasias
    • •can be caused by either 1) defective proteoglycans or 2) defective Collagen II
    • •clinical correlate: collagen II OR chondroitin proteoglycans
    • •flattened nose bridge and malformed legs, feet, toes, forearm & fingers
  14. Matricellular Proteins
    • •secreted and bound tightly to cell surface through interactions with integrins; help attach cells to each other and the ECM
    • •they help regulate proliferation, motility, and differentiation because they're attached to cytoskeleton & signaling pathways
  15. What are 3 examples of matricellular proteins?
    • 1) fibronectin
    • 2) laminin
    • 3) CCN proteins
  16. fibronectin
    type of matricellular protein found in connective tissue/mesenchymal matrices (glue for attaching cells)
  17. laminin
    matricellular protein found in basement membranes
  18. Integrins
    • Receptors for fibronectin, laminins, CCN proteins as well as other molecules; often connect to cell signaling and cytoskeletal machinery via tightly complexed proteins on cytoplasmic side of membranes
    • •"they're everywhere"
  19. Glanzmann's Thrombasthenia*
    • •clinical correlate: integrin
    • •defect of integrins in platelets; inability to clot properly
    • •autosomal recessive
  20. Elastin
    major component of the elastic laminae of large artery walls; cross-linked by fibrillin
  21. Marfan’s syndrome
    • •clinical correlate: elastin
    • •defective fibrillin fails to cross-link elastin
    • •people with Marfan's are really tall --> seen in a few basketball players
    • •upon overexertion aneurism can occur in athletes with Marfan's
  22. Cadherins
    • cell adhesion molecules important in maintaining tissue integrity (ie, skin) by connecting desmosomes of adjacent skin cells (require Ca 2+)
    • •defects in cadherins connecting desmosomes can weaken/destroy integrity of the skin and cause sloughing and blistering
    • •(critical in embryonic development)
  23. Pemphigus
    • •autoimmune blistering disease, therefore clinical correlate: cadherins
    • •antibodies against cadherins destroy desmosomes and hemidesmosomes, resulting in blisters
  24. CAMs (Cell Adhesion Molecules)
    • •basically play a role in bringing immune response to an infected EC
    • •leukocytes roll along endothelium by sticking weakly to P-selectin (a matricellular protein)
    • •if a tissue is inflamed, the endothelial cells in that area express Platelet Activating Factor (PAF), which binds to the PAF receptor ON the leukocyte --> stronger binding
    • •this binding additionally activates an integrin ON the leukocyte which itself binds tightly to ICAM-1 back to the EC membrane
    • •leukocyte stops and invades the tissue
  25. Matrix Metalloproteinases (MMPs)
    • enzymes in the matrix that bind metal ions and are responsible for breaking down collagen and the ECM
    • •required for stimulating and inhibiting angiogenesis, cancer cell metastasis, tissue remodeling, & wound healing
  26. Metastatic Cancer
    • clinical correlate: MMPs (+ fibronectin, laminin, matrix-degrading enzymes)
    • •cancer that has spread from the place where it first started to another place in the body
  27. positional control is another way to say:
    cell-matrix interactions
  28. Cardiovascular Disease: Arteriosclerosis and Restenosis
    related to most things discussed in CellBio proteoglycans, CAMs, etc)
Card Set
Cell Bio ECM (7)
Exam 1