Flashcards in Cell-cell and cell matrix interactions flashcards Deck (21):
4 ECM components
1. Collagen fibers 2. Elastin fibers 3. Proteoglycans 4. Multiadhesive matrix proteins
3 multiadhesive matrix proteins
1. Fibronectin 2. Laminin 3. Perlecan
Multiadhesive matrix glycoprotein that binds to integrins
Multiadhesive matrix major protein of ECM and basement membrane. Several functional domains which bind to cells, collagen, and other molecules-therefore can bind cells to basement membrane.
Multiadhesive matrix proteglycan which binds to and cross-links ECM components and cell-surface molecules
4 cell-adhesion molecules (CAMs)
1. Cadherins 2. Selectins 3. Integrins 4. Immunoglobin (Ig) superfamily
Calcium-dependent glycoproteins which mediate zonula adherens. Intracellular, transmembrane, and intercellular domains. 3 types: E (epithelial) cadherins, P (placental) cadherins, N (neural) cadherins. Use trypsin or EDTA (which bind calcium) to dissociate cells.
Act as linkers that directly or indirectly connect cadherins to the cytoskeleton. Recruit intracellular molecules for signaling.
Alpha and beta catenin
Types of adapter proteins which act as linkers that directly or indirectly connect cadherins to the cytoskeleton
Cadherins in cancer (3)
1. E-cadherin down-regulated and increases cellular motility, allowing cancer cells to cross basement membrane 2. Loss of E cadherin-->disintegration of cadherin-catenin complex-->Release of signal molecules that may be involved in cell invasiveness 3. N-cadherin is often up-regulated in breast cancer (not usually expressed in mammory epithelium). An N-cadherin antagonist showed dispuption of tumor vasculature, tumor growth inhibition, and apoptosis in tumor cells.
Calcium-dependent glycoproteins produced by endothelial cells and involved in inflammatory process. 3 types: E-selectin (endothelial-leukocyte adhesion molecule), P-selectin (recruitment of platelets), L-selectin (on leukocytes)
Process of selectin production
Foreign substance-->Macrophages produce cytokines-->stimulate Endothelial cells which produce selectins
How do endothelial cells recruit leukocytes?
E selectins recognize the carbohydrate and E and P selectins interact with leukocytes and slow them down, causing them to roll along vessel wall near infection site
Selectins and cancer
Overexpression of E-selectin in vascular endohelium associated with positive lymph node metastasis in breast cancer. Down-regulation of E-selectin correlates with reduction in adhesion of breast cancer cells.
Cell surface glycoproteins which act as receptors for any of the ECM components. Intracellular, transmembrane, and intercellular domains. Attach intracellular adapter proteins that mediate cytoskeleton microfilament attachment and activate adhesion-dependent bidirectional signals.
3 steps in extravasation of leukocytes
Integrins control organization of cytoskeleton for this to occur 1. E and P selectins weakly bind and cause leukocyte to roll along surface 2. ICAM-1 (Ig family) binds tightly to integrins on leukocyte surface stopping them from rolling 3. Leukocytes secrete proteases and squeeze through endothelium, breaking through basement membrane.
Rare genetic defect in synthesis of integrin subunit. Susceptible to infection, poor wound healing because leukocytes cannot extravasate, migrate, and phagocytose bacteria properly.
Integrins in cancer (3)
1. Integrin activation down-regulates E cadherins 2. modulate expression/activity of MMPs (break down matrix) 3. Target for cancer therapy
Transmembrane proteins with multiple Ig domains (repeats) in extracellular regions. Involved in immune system and in recognition, binding, and adhesion of cells. Share features with antibodies.
Autoantibodies produced against either a particular integrin or laminin in matrix. Body attacks itself resulting in blisters all over the body.