A functional interaction between the neuronal adhesion molecules TAG-1 and F3 modulates neurite outgrowth and fasciculation of cerebellar granule cells.
J. Neurosci.. 1998-09-01; 18(17): 6853-6870
DOI: 10.1523/jneurosci.18-17-06853.1998
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Buttiglione M(1), Revest JM, Pavlou O, Karagogeos D, Furley A, Rougon G, Faivre-Sarrailh C.
Author information:
(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.
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.