S. Mion et al., Bidirectional regulation of neurite elaboration by alternatively spliced metabotropic glutamate receptor 5 (mGluR5) isoforms, MOL CELL NE, 17(6), 2001, pp. 957-972
Alternative splicing in the mGluR5 gene generates two different receptor is
oforms, of which expression is developmentally regulated. However, little i
s known about the functional significance of mGluR5 splice variants. We hav
e examined the functional coupling, subcellular targeting, and effect on ne
uronal differentiation of epitope-tagged mGluR5 isoforms by expression in n
euroblastoma NG108-15 cells. We found that both mGluR5 splice variants give
rise to comparable [Ca2+](i) transients and have similar pharmacological p
rofile. Tagged receptors were shown by immunofluorescence to be inserted in
the plasma membrane. In undifferentiated cells the subcellular localizatio
n of the two mGluR5 isoforms was partially segregated, whereas in different
iated cells the labeling largely redistributed to the newly formed neurites
. Interestingly, we demonstrate that mGluR5 splice variants dramatically in
fluence the formation and maturation of neurites; mGluR5a hinders the acqui
sition of mature neuronal traits and mGluR5b fosters the elaboration and ex
tension of neurites. These effects are partly inhibited by MPEP.