A FUNCTIONAL INTERACTION BETWEEN THE NEURONAL ADHESION MOLECULES TAG-1 AND F3 MODULATES NEURITE OUTGROWTH AND FASCICULATION OF CEREBELLAR GRANULE CELLS
M. Buttiglione et al., A FUNCTIONAL INTERACTION BETWEEN THE NEURONAL ADHESION MOLECULES TAG-1 AND F3 MODULATES NEURITE OUTGROWTH AND FASCICULATION OF CEREBELLAR GRANULE CELLS, The Journal of neuroscience, 18(17), 1998, pp. 6853-6870
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 c
ultured on monolayers of transfected Chinese hamster ovary (CHO) cells
, we show that F3 and TAG-1 interact functionally. F3 transfectants ha
ve been shown to in hibit outgrowth and induce fasciculation of granul
e cell neurites. By contrast TAG-1 transfectants have no effect on the
se 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 n
euronal receptor, and in favor of this we observed that binding sites
for microspheres conjugated with F3 and TAG-1 are colocalized on the g
ranule cell growth cones, (2) or alternatively, F3 and TAG-1 associate
in a multimolecular complex after their binding to independent recept
ors. Extensive co-clustering of F3 with TAG-1 can in fact be achieved
by anti-TAG-1 antibody-mediated cross-linking in double-transfected CH
O cells. Moreover, F3 coimmunoprecipitates with TAG-1 in Triton X-100-
insoluble microdomains purified from newborn brain. These data strongl
y suggest that F3 and TAG-1 may associate under physiological conditio
ns to modulate neurite outgrowth and fasciculation of the cerebellar g
ranule cells.