Blog
About

61
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      α-Actinin-4/FSGS1 is required for Arp2/3-dependent actin assembly at the adherens junction

      ,

      The Journal of Cell Biology

      The Rockefeller University Press

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          α-Actinin-4 plays an important role in coupling actin nucleation to assembly at cadherin-based cell–cell adhesive contacts.

          Abstract

          We have developed an in vitro assay to study actin assembly at cadherin-enriched cell junctions. Using this assay, we demonstrate that cadherin-enriched junctions can polymerize new actin filaments but cannot capture preexisting filaments, suggesting a mechanism involving de novo synthesis. In agreement with this hypothesis, inhibition of Arp2/3-dependent nucleation abolished actin assembly at cell–cell junctions. Reconstitution biochemistry using the in vitro actin assembly assay identified α-actinin-4/focal segmental glomerulosclerosis 1 (FSGS1) as an essential factor. α-Actinin-4 specifically localized to sites of actin incorporation on purified membranes and at apical junctions in Madin–Darby canine kidney cells. Knockdown of α-actinin-4 decreased total junctional actin and inhibited actin assembly at the apical junction. Furthermore, a point mutation of α-actinin-4 (K255E) associated with FSGS failed to support actin assembly and acted as a dominant negative to disrupt actin dynamics at junctional complexes. These findings demonstrate that α-actinin-4 plays an important role in coupling actin nucleation to assembly at cadherin-based cell–cell adhesive contacts.

          Related collections

          Most cited references 76

          • Record: found
          • Abstract: found
          • Article: not found

          Cell adhesion: the molecular basis of tissue architecture and morphogenesis.

           B Gumbiner (1996)
          A variety of cell adhesion mechanisms underlie the way that cells are organized in tissues. Stable cell interactions are needed to maintain the structural integrity of tissues, and dynamic changes in cell adhesion participate in the morphogenesis of developing tissues. Stable interactions actually require active adhesion mechanisms that are very similar to those involved in tissue dynamics. Adhesion mechanisms are highly regulated during tissue morphogenesis and are intimately related to the processes of cell motility and cell migration. In particular, the cadherins and the integrins have been implicated in the control of cell movement. Cadherin mediated cell compaction and cellular rearrangements may be analogous to integrin-mediated cell spreading and motility on the ECM. Regulation of cell adhesion can occur at several levels, including affinity modulation, clustering, and coordinated interactions with the actin cytoskeleton. Structural studies have begun to provide a picture of how the binding properties of adhesion receptors themselves might be regulated. However, regulation of tissue morphogenesis requires complex interactions between the adhesion receptors, the cytoskeleton, and networks of signaling pathways. Signals generated locally by the adhesion receptors themselves are involved in the regulation of cell adhesion. These regulatory pathways are also influenced by extrinsic signals arising from the classic growth factor receptors. Furthermore, signals generated locally be adhesion junctions can interact with classic signal transduction pathways to help control cell growth and differentiation. This coupling between physical adhesion and developmental signaling provides a mechanism to tightly integrate physical aspects of tissue morphogenesis with cell growth and differentiation, a coordination that is essential to achieve the intricate patterns of cells in tissues.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Regulation of cadherin-mediated adhesion in morphogenesis.

            Cadherin cell-adhesion proteins mediate many facets of tissue morphogenesis. The dynamic regulation of cadherins in response to various extracellular signals controls cell sorting, cell rearrangements and cell movements. Cadherins are regulated at the cell surface by an inside-out signalling mechanism that is analogous to the integrins in platelets and leukocytes. Signal-transduction pathways impinge on the catenins (cytoplasmic cadherin-associated proteins), which transduce changes across the membrane to alter the state of the cadherin adhesive bond.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Cell surface mechanics and the control of cell shape, tissue patterns and morphogenesis.

              Embryonic morphogenesis requires the execution of complex mechanisms that regulate the local behaviour of groups of cells. The orchestration of such mechanisms has been mainly deciphered through the identification of conserved families of signalling pathways that spatially and temporally control cell behaviour. However, how this information is processed to control cell shape and cell dynamics is an open area of investigation. The framework that emerges from diverse disciplines such as cell biology, physics and developmental biology points to adhesion and cortical actin networks as regulators of cell surface mechanics. In this context, a range of developmental phenomena can be explained by the regulation of cell surface tension.
                Bookmark

                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                9 January 2012
                : 196
                : 1
                : 115-130
                Affiliations
                Department of Cell and Developmental Biology, University of Illinois, Urbana, IL 61801
                Author notes
                Correspondence to William M. Brieher: wbrieher@ 123456illinois.edu
                Article
                201103116
                10.1083/jcb.201103116
                3255975
                22232703
                © 2012 Tang and Brieher

                This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                Product
                Categories
                Research Articles
                Article

                Cell biology

                Comments

                Comment on this article