QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anilkumar, N. Articles by Adams, J. C. Search for Related Content PubMed PubMed Citation Articles by Anilkumar, N. Articles by Adams, J. C. Social Bookmarking                         What's this?

Trimeric assembly of the C-terminal region of Thrombospondin-1 or Thrombospondin-2 is necessary for cell spreading and fascin spike organisation

Narayanapanicker Anilkumar¹, Douglas S. Annis², Deane F. Mosher² and Josephine C. Adams^1,*,

¹ MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, London, WC1E 6BT, UK
² Department of Medicine, University of Wisconsin, Madison, WI 53706, USA
Present address: Department of Cell Biology, NC1-110, Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195, USA

^* Author for correspondence (e-mail: adamsj{at}ccf.org )

Accepted 12 March 2002

Thrombospondin-1 (TSP-1) and the highly related protein thrombospondin-2 (TSP-2) are trimeric extracellular molecules that have complex roles in wound healing, angiogenesis and matrix organisation. At the cellular level, TSP-1 supports cell adhesion and migration by the organisation of fascin spike cytoskeletal structures. To define the molecular requirements for assembly of fascin spikes by thrombospondins, we developed a panel of recombinant protein units of TSP-1 and TSP-2; these were designed according to the domain boundaries and included matched monomeric and trimeric units. These proteins were tested for their effects on cell attachment and fascin spike organisation using C2C12 skeletal myoblasts and vascular smooth muscle cells. In monomeric units, cell attachment activity was localised to the type 1 repeats or type 3 repeats/C-terminal globule, and both regions need to be present in the same molecule for maximal activity. On a molar basis, cell-attachment activities with monomeric units were low compared with intact TSP-1, and no monomeric unit induced cell spreading. Trimeric versions of the type 1 repeats were more adhesive but did not induce cell spreading. Strikingly, trimers that contained the type 3 repeats/C-terminal globule of either TSP-1 or TSP-2 supported cell spreading and fascin spike organisation, producing a similar activity to intact TSP-1. We conclude that trimeric assembly of the highly conserved TSP C-terminal region is necessary for organisation of the fascin-based cytoskeletal structures that are needed for thrombospondin-induced cell motility.

Key words: Cell adhesion, Extracellular matrix, Oligomerisation, Actin cytoskeleton, Fascin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				M. A. Pallero, C. A. Elzie, J. Chen, D. F. Mosher, and J. E. Murphy-Ullrich Thrombospondin 1 binding to calreticulin-LRP1 signals resistance to anoikis FASEB J, November 1, 2008; 22(11): 3968 - 3979. [Abstract] [Full Text] [PDF]

				G. Martin-Manso, S. Galli, L. A. Ridnour, M. Tsokos, D. A. Wink, and D. D. Roberts Thrombospondin 1 Promotes Tumor Macrophage Recruitment and Enhances Tumor Cell Cytotoxicity of Differentiated U937 Cells Cancer Res., September 1, 2008; 68(17): 7090 - 7099. [Abstract] [Full Text] [PDF]

				Y. Hashimoto, M. Parsons, and J. C. Adams Dual Actin-bundling and Protein Kinase C-binding Activities of Fascin Regulate Carcinoma Cell Migration Downstream of Rac and Contribute to Metastasis Mol. Biol. Cell, November 1, 2007; 18(11): 4591 - 4602. [Abstract] [Full Text] [PDF]

				O. I. Stenina, E. J. Topol, and E. F. Plow Thrombospondins, Their Polymorphisms, and Cardiovascular Disease Arterioscler. Thromb. Vasc. Biol., September 1, 2007; 27(9): 1886 - 1894. [Abstract] [Full Text] [PDF]

				S. A. Kuznetsova, P. Issa, E. M. Perruccio, B. Zeng, J. M. Sipes, Y. Ward, N. T. Seyfried, H. L. Fielder, A. J. Day, T. N. Wight, et al. Versican-thrombospondin-1 binding in vitro and colocalization in microfibrils induced by inflammation on vascular smooth muscle cells J. Cell Sci., November 1, 2006; 119(21): 4499 - 4509. [Abstract] [Full Text] [PDF]

				S. A. Kuznetsova, A. J. Day, D. J. Mahoney, M. S. Rugg, D. F. Mosher, and D. D. Roberts The N-terminal Module of Thrombospondin-1 Interacts with the Link Domain of TSG-6 and Enhances Its Covalent Association with the Heavy Chains of Inter-{alpha}-trypsin Inhibitor J. Biol. Chem., September 2, 2005; 280(35): 30899 - 30908. [Abstract] [Full Text] [PDF]

				M. J. Calzada, D. S. Annis, B. Zeng, C. Marcinkiewicz, B. Banas, J. Lawler, D. F. Mosher, and D. D. Roberts Identification of Novel {beta}1 Integrin Binding Sites in the Type 1 and Type 2 Repeats of Thrombospondin-1 J. Biol. Chem., October 1, 2004; 279(40): 41734 - 41743. [Abstract] [Full Text] [PDF]