• M Bamdad, D Volle, B Dastugue, and A Meiniel.
• Faculté de Médecine, UMR INSERM 384 et Laboratoire de Biochimie médicale, 28 place Henri-Dunant, BP 38, 63001, Clermont-Ferrand Cedex, France.
• Cell Tissue Res. 2004 Jan 1; 315 (1): 15-25.

AbstractIn the central and peripheral nervous systems a heterogeneous group of proteins constituting the thrombospondin superfamily provides a cue for axonal pathfinding. They either contain or are devoid of the tripeptide RGD, and the sequence(s) and mechanism(s) which trigger in vitro their neurite-promoting activity have remained unclear. In this study, we reconsider the problem of whether sequences present in the thrombospondin type 1 repeats (TSRs), and independent of the well-known RGD-binding site, may activate integrins and account for their neurite-promoting activity. SCO-spondin is a newly identified member of the thrombospondin superfamily, which shows a multidomain organization with a great number of TSR motifs but no RGD sequence. Previous research has implicated oligopeptides derived from SCO-spondin TSRs in in-vitro development of various neuronal cell types. In this study, we investigate whether function-blocking antibodies directed against integrin subunits can block these effects in cell line B104, cloned from a neuroblastoma of the rat central nervous system. By two different approaches: flow cytometry revealing short-term effects and cell cultures revealing long-term effects, we show that: (a). activation of cell metabolism, (b). changes in cell size and structure, and (c). neurite-promoting activity induced by TSR oligopeptides are inhibited by function-blocking antibodies to beta1-subunit. Using a panel of function-blocking antibodies directed against various integrin alpha-subunits we show that the alpha1-subunit might be the partner of the beta1-subunit in B104 cells. Thus, we demonstrate that an original sequence within a TSR motif from SCO-spondin promotes neurite outgrowth through an intracellular signal driven by integrins, independently of an RGD-binding site.

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