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CONTACT INFORMATION: LUISA IRUELA-ARISPE MBI/BOYER HALL 559 PHONE# 310 - 794-5763

CELL-CELL INTERACTIONS Lecture 2 January 11th, 2006. CONTACT INFORMATION: LUISA IRUELA-ARISPE MBI/BOYER HALL 559 PHONE# 310 - 794-5763 arispe@mbi.ucla.edu. Heterotypic. Homotypic. 1) Inflammation - Leukocyte recruitment. integrins. ICAM. Endothelial-Leukocyte. 2) Implantation.

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CONTACT INFORMATION: LUISA IRUELA-ARISPE MBI/BOYER HALL 559 PHONE# 310 - 794-5763

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  1. CELL-CELL INTERACTIONS Lecture 2 January 11th, 2006 CONTACT INFORMATION: LUISA IRUELA-ARISPE MBI/BOYER HALL 559 PHONE# 310 - 794-5763 arispe@mbi.ucla.edu

  2. Heterotypic Homotypic 1) Inflammation - Leukocyte recruitment integrins ICAM Endothelial-Leukocyte 2) Implantation VCAM Endometrial epithelium a4b1 blastocyst 3) Fertilization Fertile sperm EGG a6b1 Association between epithelial cells

  3. Cell-Cell Interactions are Mediated by Four Major Families of Proteins Cadherins E-Cadherins -- Epithelial N-Cadherins -- Neuronal VE-Cadherins -- Vascular Endothelium P-Cadherins -- Placenta 2) Some members of the IgSF (Immunoglobulin Super Family) 3) Some members of the IgSF (Immunoglobulin Super Family) 4) Selectin

  4. Cadherins mediate homotypic interactions • Epithelial cells can recognize each other and form layers of attached cells due to interactions mediated by cell surface E-cadherin molecules. Calcium is required for cadherin interactions. Ca++ ions are situated between the domains of the cadherin molecules and provide rigidity to the extracellular position of the protein.

  5. attachment membranes Organization of cadherinsDesmosomes - Molecular Structure Desmosomes are formed in specialized areas of cells - the cytoplasmic side contains tonofilamers that are anchored in a plaque of proteins. Cadherin molecules provide the cell - cell interactions.

  6. Structure of Hemidesmosomes (a6b4) Hemidesmosomes connect epithelial cells to the basal lamina. The integrin a6b4 binds to proteins in the plaques and to laminin in the extracellular matrix.

  7. Cadherins in Adherens Junctions Protein linking b-catenin to cytoskeleton • In adherens junctions actin filaments are connected to the cyoplasmic side of cadherin molecules via b-catenins.

  8. Cadherin signaling

  9. Cadherin signaling pathways

  10. Regulation of beta-catenin by Wnt signaling

  11. Participation of Cadherins in multiple cellular events

  12. Selectins • Selectins are cell-adhesion molecules that recognize specific carbohydrate groups at the ends of oligosaccharide chains of glycoproteins present in other cells.

  13. Cell Adhesion Is Important during Inflammation • Activation of endothelial cells increases levels of selectins that bind to neutrophils and together with ICAM mediate neutrophil diapedeses atsites of inflammation.

  14. Selectins: Tethering and Rolling

  15. Selectin-Carbohydrate

  16. Integrins: Sticking and Crawling

  17. Integrins and their IgSF Ligands LFA-1 47 Mac-1 41

  18. Multi-Step Model Tethering/Rolling Firm Adhesion Diapedesis Chemotaxis Selectins Integrins Flow

  19. Leukocyte-Endothelial Adhesion Molecule-Deficient Mice • LFA-1 • Mac-1 • CD18 (2) • VLA-4 • 1 • ICAM-1 • VCAM-1 • PECAM-1 • P-selectin • E-selectin • L-selectin • E-, P-, L-selectin • FucT-IV and VII

  20. Human Leukocyte Adhesion Deficiency (LAD) Syndromes • LAD I- deficiency of the major leukocyte 2 integrin adhesion complex (CD11/CD18) • LAD II- defect in fucose metabolism resulting in deficiency of selectin ligands • LAD III - defect in 1, 2, and 3 integrin activation

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