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Published byBritton Peters Modified over 9 years ago
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Cell-cell adhesion occurs through morphological structures and CAMs
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Cell adhesion is a dynamic Process that plays an important role in embryo development
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Cell-cell adhesion is tissue-specific
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Molecular structure of Cadherins 1. Cadherin was identified via monoclonal antibody generation and in vitro aggregation assays 2. E-cadherin was named also as uvomorulin
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Cadherin binds each other via homophilic binding
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Mode of cadherin interaction
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Expression of cadherin is dynamically controlled during embryogenesis
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Catenins are adaptor proteins that bind cadherin to actin cytoskeleton
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Binding sites for classical cadherin
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-catenin occurs both at cell adhesion site and within nucleus
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Phosphorylated -catenin is degraded through ubiquitination pathway
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Nuclear -catenin enhances cell proliferation
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Mutated APC complex promotes entry of -catenin into nucleus and enhances cell proliferation
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Inappropriate expression of -catenin induces cell cycle progression in intestine
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-catenin binds diverse proteins
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Molecular structure of N-CAM 1.N-CAM comprises 5 Ig-like extracellular domains 2. Mode of binding is via heterophilic interaction
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Molecular structure of Selectin
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Classification of cell junctions
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Components of junctional complex
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General structure of anchoring junctions
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Intermediate junction (adhesion belt)
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E-cadherin constitutes the core of intermediate junction
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Desmosome
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Molecular components of desmosomes
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Desmosomes connect epithelial cells as a whole
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Tight junctions prevent passage of extracellular material into intracellular space
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Molecular components of hemidesmsomes
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Cell adhesion needs cytoskeleton
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Gap junctions are made up of connexons with a 2nm intracellular gap
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Each connexon is made of 6 subunits (connexin) and controls passage of molecules with MW < 1000 Da
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Cell-matrix interaction
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Extracellular matrix reorganizes cytoskeleton of transformed cells
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Integrin functions as linking molecule for ECM and cytoskeleton
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Colocalization of integrin and actin cytoskeleton
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Molecular structure of Integrin
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Focal adhesion Focal complex Focal contacts
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Rac dependent formation of focal complex
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Dentritic network model of actin assembly
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Molecular constitutents of focal complex
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How focal complex is assembled into focal contact ? ? ?
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Rho dependent growth of focal contacts
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Myosin light chain (MLC) phosphorylation is modulated by Rho
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Assembly of focal contact is mediated through integrin clustering and formation of stress fibers
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Feedback loop controlling the formation and growth of focal contacts FAK Src
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Basic rules that regulate the fate of a focal contact 1. initially binding of integrins to their ECM partners takes place at the leading edge 2. Rac is activated and drives the formation of focal complex by activating the assembly of dynamic actin network in the lamellipodium 3. Rho drives the maturation of focal contacts by the activation of both Dia and ROCK 4. Pulling of focal contacts promotes tension-dependent incorporation of new components into the nascent adhesion sites, leading to its growth
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Anoikis: type of apoptosis for cells that denied adhesion
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Integrins transmit signals through ligation-dependent recruitment of non-receptor tyrosine kinase from the focal adhesion kinase (FAK) and Src
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Integrin-mediated resistance to stress-induced apoptosis via Ras-PI3-kinase-Akt pathway
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Role of ERK activation in integrin resistance to stress- induced apoptosis
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FAK regulates cellular locomotion
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Deficiency of FAK results in arrest of cell movement
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