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Journal of Cell Science 115, 2357-2366 (2002)
© 2002 The Company of Biologists Limited

Research Article

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. Adams1,*,{ddagger}

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
{ddagger} 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




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© The Company of Biologists Ltd 2002