49
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A crucial role for β2 integrins in podosome formation, dynamics and Toll-like-receptor-signaled disassembly in dendritic cells

      research-article

      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

          The dynamic properties of podosomes, their ability to degrade the underlying matrix and their modulation by Toll-like receptor (TLR) signaling in dendritic cells (DCs) suggests they have an important role in migration. Integrins are thought to participate in formation and dynamics of podosomes but the multiplicity of integrins in podosomes has made this difficult to assess. We report that murine DCs that lack β2 integrins fail to form podosomes. Re-expression of β2 integrins restored podosomes but not when the membrane proximal or distal NPxF motifs, or when an intervening triplet of threonine residues were mutated. We show that β2 integrins are remarkably long-lived in podosome clusters and form a persistent framework that hosts multiple actin-core-formation events at the same or adjacent sites. When β2 integrin amino acid residues 745 or 756 were mutated from Ser to Ala, podosomes became resistant to dissolution mediated through TLR signaling. TLR signaling did not detectably modulate phosphorylation at these sites but mutation of either residue to phospho-mimetic Asp increased β2 integrin turnover in podosomes, indicating that phosphorylation at one or both sites establishes permissive conditions for TLR-signaled podosome disassembly.

          Related collections

          Most cited references37

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

          The 'ins' and 'outs' of podosomes and invadopodia: characteristics, formation and function.

          Podosomes and invadopodia are actin-based dynamic protrusions of the plasma membrane of metazoan cells that represent sites of attachment to - and degradation of - the extracellular matrix. The key proteins in these structures include the actin regulators cortactin and neural Wiskott-Aldrich syndrome protein (N-WASP), the adaptor proteins Tyr kinase substrate with four SH3 domains (TKS4) and Tyr kinase substrate with five SH3 domains (TKS5), and the metalloprotease membrane type 1 matrix metalloprotease (MT1MMP; also known as MMP14). Many cell types can produce these structures, including invasive cancer cells, vascular smooth muscle and endothelial cells, and immune cells such as macrophages and dendritic cells. Recently, progress has been made in our understanding of the regulatory and functional aspects of podosome and invadopodium biology and their role in human disease.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The tail of integrins, talin, and kindlins.

            Integrins are transmembrane cell-adhesion molecules that carry signals from the outside to the inside of the cell and vice versa. Like other cell surface receptors, integrins signal in response to ligand binding; however, events within the cell can also regulate the affinity of integrins for ligands. This feature is important in physiological situations such as those in blood, in which cells are always in close proximity to their ligands, yet cell-ligand interactions occur only after integrin activation in response to specific external cues. This review focuses on the mechanisms whereby two key proteins, talin and the kindlins, regulate integrin activation by binding the tails of integrin-beta subunits.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The matrix corroded: podosomes and invadopodia in extracellular matrix degradation.

              Podosomes and invadopodia are unique actin-rich adhesions that establish close contact to the substratum but can also degrade components of the extracellular matrix. Accordingly, matrix degradation localized at podosomes or invadopodia is thought to contribute to cellular invasiveness in physiological and pathological situations. Cell types that form podosomes include monocytic, endothelial and smooth muscle cells, whereas invadopodia have been mostly observed in carcinoma cells. This review highlights important new developments in the field, discusses the common and divergent features of podosomes and invadopodia and summarizes current knowledge about matrix-degrading proteinases at these structures.
                Bookmark

                Author and article information

                Journal
                J Cell Sci
                J. Cell. Sci
                joces
                jcs
                Journal of Cell Science
                The Company of Biologists (Bidder Building, 140 Cowley Road, Cambridge, CB4 0DL, UK )
                0021-9533
                1477-9137
                1 October 2014
                1 October 2014
                : 127
                : 19
                : 4213-4224
                Affiliations
                [1 ]Division of Cell Biology and Immunology, College of Life Sciences, University of Dundee , Dundee DD1 5EH, UK
                [2 ]University of Dundee, Ninewells Hospital and Medical School , Dundee DD1 9SY, UK
                [3 ]MRC Protein Phosphorylation and Ubiquitylation Unit, College of Life Sciences, University of Dundee , Dundee DD1 5EH, UK
                Author notes
                [*]

                Present address: Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, UK.

                [‡]

                Present address: Institute of Biotechnology, P.O. Box 56, University of Helsinki, 00014 Helsinki. Finland.

                [§]

                These authors contributed equally to this work

                []Author for correspondence ( c.watts@ 123456dundee.ac.uk )
                Article
                10.1242/jcs.151167
                4179490
                25086067
                0fda86d8-0b40-441f-81e3-71d7b797a5e2
                © 2014. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 7 February 2014
                : 7 July 2014
                Categories
                Research Article
                124

                Cell biology
                podosomes,dendritic cells,integrins
                Cell biology
                podosomes, dendritic cells, integrins

                Comments

                Comment on this article