The Journal of Neuroscience, June 1, 1998, 18(11):4189-4200
G Protein-Mediated Inhibition of Neuronal Migration Requires
Calcium Influx
Angela M.
Horgan and
Philip F.
Copenhaver
Department of Cell and Developmental Biology, Oregon Health
Sciences University, Portland, Oregon 97201
Neuronal migration is an essential feature of the developing
nervous system, but the intracellular signaling mechanisms that regulate this process are poorly understood. During the formation of
the enteric nervous system (ENS) in the moth Manduca
sexta, the migration of an identified set of neurons (the EP
cells) is regulated in part by the heterotrimeric guanyl-nucleotide
binding protein (G protein) Go
. Using an in
vivo culture preparation for developing embryos that allows
direct access to the ENS, we have shown that EP cell migration is
similarly regulated by intracellular Ca2+;
treatments that increased intracellular Ca2+
inhibited the migratory process, whereas buffering intracellular Ca2+ induced aberrant migration onto inappropriate
pathways. Imaging the spontaneous changes in intracellular
Ca2+ within individual EP cells showed that actively
migrating neurons exhibited only small fluctuations in intracellular
Ca2+. In contrast, neurons that had reached the end
of migration displayed large, transient Ca2+ spikes.
Similar Ca2+ spikes were induced in the EP cells by
G protein stimulation, an effect that was reversed by removal of
external Ca2+. Stimulation of Go in
individual EP cells (by injection of either activated Go
subunits or mastoparan) also inhibited migration in a
Ca2+-dependent manner. These results suggest that
the regulation of neuronal migration by G proteins involves a
Ca2+-dependent process requiring
Ca2+ influx.
Key words:
G protein; neuronal migration; neuronal guidance; calcium; Manduca sexta; embryonic development
Copyright © 1998 Society for Neuroscience 0270-6474/98/18114189-12$05.00/0
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