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The Journal of Neuroscience, September 1, 1998, 18(17):6853-6870

A Functional Interaction between the Neuronal Adhesion Molecules TAG-1 and F3 Modulates Neurite Outgrowth and Fasciculation of Cerebellar Granule Cells

Maura Buttiglione¹, Jean-Michel Revest¹, Ourania Pavlou², Domna Karagogeos², Andrew Furley³, Geneviève Rougon¹, and Catherine Faivre-Sarrailh¹

¹ Laboratoire de Génétique et de Physiologie du Développement, UMR 6545 Centre National de la Recherche Scientifique, Institut de Biologie du Développement de Marseille, Parc Scientifique de Luminy, 13288 Marseille cedex 9, France, ² Department of Basic Science, University of Crete Medical School and Institute of Molecular Biology and Biotechnology, Heraklion, 71110 Crete, Greece, and ³ Developmental Genetics Programme, University of Sheffield, Sheffield S10 2TN, England

F3 and TAG-1 are two closely related adhesion glycoproteins of the Ig superfamily that are both expressed by the axons of cerebellar granule cells. In an in vitro system in which cerebellar granule cells were cultured on monolayers of transfected Chinese hamster ovary (CHO) cells, we show that F3 and TAG-1 interact functionally. F3 transfectants have been shown to inhibit outgrowth and induce fasciculation of granule cell neurites. By contrast TAG-1 transfectants have no effect on these events. However, when TAG-1 is coexpressed with F3, the inhibitory effect of F3 is blocked. Two possible mechanisms may account for this functional interaction: (1) either TAG-1 and F3 compete for the same neuronal receptor, and in favor of this we observed that binding sites for microspheres conjugated with F3 and TAG-1 are colocalized on the granule cell growth cones, (2) or alternatively, F3 and TAG-1 associate in a multimolecular complex after their binding to independent receptors. Extensive co-clustering of F3 with TAG-1 can in fact be achieved by anti-TAG-1 antibody-mediated cross-linking in double-transfected CHO cells. Moreover, F3 coimmunoprecipitates with TAG-1 in Triton X-100-insoluble microdomains purified from newborn brain. These data strongly suggest that F3 and TAG-1 may associate under physiological conditions to modulate neurite outgrowth and fasciculation of the cerebellar granule cells.

Key words: F3/F11; TAG-1; microdomains; neuronal adhesion glycoprotein; cerebellum; granule cell culture; axonal outgrowth; fasciculation

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Copyright © 1998 Society for Neuroscience  0270-6474/98/18176853-18$05.00/0

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