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      Integration of signaling and cytoskeletal remodeling by Nck in directional cell migration

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          Abstract

          Planar and apical-basal cellular polarization of epithelia and endothelia are crucial during morphogenesis. The establishment of these distinct polarity states and their transitions are regulated by signaling networks that include polarity complexes, Rho GTPases, and phosphoinositides. The spatiotemporal coordination of signaling by these molecules modulates cytoskeletal remodeling and vesicle trafficking to specify membrane domains, a prerequisite for the organization of tissues and organs. Here we present an overview of how activation of the WASp/Arp2/3 pathway of actin remodeling by Nck coordinates directional cell migration and speculate on its role as a signaling integrator in the coordination of cellular processes involved in endothelial cell polarity and vascular lumen formation.

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          Most cited references99

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          Cellular motility driven by assembly and disassembly of actin filaments.

          Motile cells extend a leading edge by assembling a branched network of actin filaments that produces physical force as the polymers grow beneath the plasma membrane. A core set of proteins including actin, Arp2/3 complex, profilin, capping protein, and ADF/cofilin can reconstitute the process in vitro, and mathematical models of the constituent reactions predict the rate of motion. Signaling pathways converging on WASp/Scar proteins regulate the activity of Arp2/3 complex, which mediates the initiation of new filaments as branches on preexisting filaments. After a brief spurt of growth, capping protein terminates the elongation of the filaments. After filaments have aged by hydrolysis of their bound ATP and dissociation of the gamma phosphate, ADF/cofilin proteins promote debranching and depolymerization. Profilin catalyzes the exchange of ADP for ATP, refilling the pool of ATP-actin monomers bound to profilin, ready for elongation.
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            Endothelial cell migration during angiogenesis.

            Endothelial cell migration is essential to angiogenesis. This motile process is directionally regulated by chemotactic, haptotactic, and mechanotactic stimuli and further involves degradation of the extracellular matrix to enable progression of the migrating cells. It requires the activation of several signaling pathways that converge on cytoskeletal remodeling. Then, it follows a series of events in which the endothelial cells extend, contract, and throw their rear toward the front and progress forward. The aim of this review is to give an integrative view of the signaling mechanisms that govern endothelial cell migration in the context of angiogenesis.
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              Random versus directionally persistent cell migration.

              Directional migration is an important component of cell motility. Although the basic mechanisms of random cell movement are well characterized, no single model explains the complex regulation of directional migration. Multiple factors operate at each step of cell migration to stabilize lamellipodia and maintain directional migration. Factors such as the topography of the extracellular matrix, the cellular polarity machinery, receptor signalling, integrin trafficking, integrin co-receptors and actomyosin contraction converge on regulation of the Rho family of GTPases and the control of lamellipodial protrusions to promote directional migration.
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                Author and article information

                Journal
                Bioarchitecture
                Bioarchitecture
                BIOA
                Bioarchitecture
                Landes Bioscience
                1949-0992
                1949-100X
                01 May 2013
                17 July 2013
                17 July 2013
                : 3
                : 3
                : 57-63
                Affiliations
                Department of Veterinary Pathobiology; Texas A&M University; College Station, TX USA
                Author notes
                [* ]Correspondence to: Gonzalo M. Rivera, Email: GRivera@ 123456cvm.tamu.edu
                Article
                2013BIOARCHITECTURE0013R 25744
                10.4161/bioa.25744
                3782540
                23887203
                962af0dc-fae0-4062-b95f-86074ff5086b
                Copyright © 2013 Landes Bioscience

                This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.

                History
                : 30 June 2013
                : 12 July 2013
                : 12 July 2013
                Categories
                Mini Review

                Molecular biology
                nck,actin polymerization,cell migration,cell polarity,adhesion dynamics,wasp,morphogenesis,endothelial cell

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