Medical Cell Biology
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| Cell Adhesion | The binding of a cell to a surface, extracellular matrix or another cell using adhesion molecules
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| Cell Adhesion Molecules | Selectins, Integrins, and Cadherins
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| Why is cell adhesion important? | Cell adhesion is important for compartmentalization, tissue integrity, cell-cell communication, and morphogenesis
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| Cell adhesion should not occur in what surface? | APICAL SURFACE!
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| Cadherins | Epithelial cell's CAM. Needed for embryonic development. Cell-cell adhesion. Calcium dependent. Binds to cantenins in cytoplasm.
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| B-catenin | Function in signaling (WNT)
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| A-catenin | Bind to actin filament
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| Disruption of B-catenin and E-cadherin consequence? | Neoplasia of breast and colon cancer
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| Immunoglobulin Superfamily | Homophillic and heterophillic binding. Cell-cell and cell-cell-ECM. Epithelial cells-Nectin. Endothelial cells-ICAM and VCAM, which binds to integrins. Bind to cytoskeleton (actin, a-actinin, spectrin). Required disulfide bonds.
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| Afidin | Acts like b-catenin, it is a cytoplasmic binding protein for the immunoglobulin superfamily.
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| Selectins | Heterophilic binding. Cell-cell adhesion. Bind to carbohydrate on opposite cell. Calcium dependent. Cytoplasmic domain interact with actin cytoskeleton. Need for initiating adhesion of leukocytes and platelets to endothelial cells during inflamation.
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| L-selectins | Needed for tethering and rolling "Homing receptor"
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| Integrins | Cell-Cell, Cell-ECM adhesion. Low affinity state stabilized by Calcium = does not bind to ligand = Inactive. High affinity state Mn2+ and Mg2+, binds ligand = Active
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| LAD (leukocyte adhesion deficiency) | Mutations in integrins, can't make pus = Death
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| Intracellular Junctions | Tight Junction (zonula occludens), Adherens jucntion (zonula adherens), Desmosomes, Gap Junction, Hemidesmosome, Focal contact.
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| Tight Junction (Zonula Occludens) | Separates apical from intracellular space and basal surface, Contact b/w TM proteins "membrane kisses" -- claudin and occludin, Forms seal b/w adjacent epithelial cells, Regulate selective diffusion of hydrophobic molecules, Maintain cell polarity
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| ZO proteins | link TM proteins to actin cytoskeleton
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| Adherens Junction (Zonula adherens) | Located underneath tight junction, require e-cadherins (cell-cell adhesion), Ca+ dependent, associated with nectin and a-actinin, stabilized by desmosomes, help resist mechanical stress and maintain tissue integrity
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| Desmosome (macula adherens) | Cell-cell communication, found in stratified squamous epithelial of skin, need for closure of wound
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| Pemphigus Vulgaris | Autoimmune disorder of skin and mouth. Acquire antibodies agains DESMOGLEIN (desmosomal cadherins), non healing BLISTERS and sores
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| GAP Junction (NEXUS) | Hydrophilic channel allow direct exchange of small metabolites and signaling molecules b/w cells, Cell-Cell communication, 1kDA can pass, formed by 2 Connexons, contains protein called CONNEXIN
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| Oculodentodigital Dysplasia | Mutations in gene coding for CONNEXINS, Gap junction less abundant, Affect EYES, TEETH, HAND and FEET.
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| Hemidesmosomes | Integrins (a6B4) form major adhesion molecule. Integrins interact with anchoring filaments (Laminin-5) and then interact with anchoring fibrils (Col VII). Absence leads dermoepidermal separation
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| Epidermolysis Bullosa | Inherited, BLISTERING disorder of skin or mucosa, Mutations in genes coding for HEMIDESMOSOMAL PROTEINS (LAMININ 5)
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| Bullous Pemphigoid | Autoimmune, blistering skin disease- causes separation b/w cell-ECM layer
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| Focal Contact | Links actin cytoskeleton to ECM components. Cell-ECM communication. Functions to mediate dynamic attachment b/w cell and substratum. Important cell migration, wound healing, signal detection and transduction)
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| Leukocyte Adhesion, Extravasation, and Migration | leukocyte tethers (SELECTIN) -- binds to endothelium (INTEGRINS-ICAM) -- Extravasation from blood vessel (JAM, PECAM)--Migrates to source of injury (INTEGRINS)
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| Platelet Activation is enhanced by which protein | TXA2
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| Activated platelet secretes what protein | vWF -- Adhesion occur -- collagen activate platelet when leak in blood vessels
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| ERK (Extracellular signal regulated kinases) | Helps regulate proliferation of cells attachment to substratum
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| Anoikis | Regulate cells to release from substratum and undergo apoptosis
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| Bernard-Soulier Syndrome | Heriditary bleeding disorder, platelet disorder, defect in non-integrins adhesion complex, Giant platelets, LOW PLATELET COUNT (thrombocytopenia)
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| Glanzmann's Thrombasthenia | Heriditary bleeding disorder, platelet disorder, Defect in integrin adhesion receptor, poor clot retraction, NORMAL PLATELET COUNT
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