New Modes of GPCR Signalling

ABSTRACT
Manipulation of Rac Activity and Cell Motility in vivo Using Light
Xiaobo Wang, Li He, Yi Wu, Klaus Hahn and Denise J. Montell
Department of Biological Chemistry, Center for Cell Dynamics Johns Hopkins School
of Medicine, Baltimore, USA
The small GTPase Rac induces actin polymerization, membrane ruffling and focal
contact formation in cultured single cells, can promote growth cone guidance, dynamic
dendrite growth and has been implicated in learning and memory. Recently,
photoactivatable analogues of Rac (PA-Rac) have been developed, allowing rapid and
reversible activation or inactivation of Rac using light. In cultured single cells,
light-activated Rac leads to focal membrane ruffling, protrusion and migration. Here we
report that focal activation of Rac is effective in vivo. Light-mediated activation of
Rac in one part of one cell caused local ruffling and protrusion. Moreover, activation
or inactivation of Rac in one cell of a cluster caused a dramatic response in the other
cells, and set the direction of movement for the whole group. These results suggest
that the cells sense direction as a group according to relative levels of Rac activity.
Communication between cells of the cluster required Jun N-terminal kinase (JNK) but
not guidance receptor signalling. These studies further suggest that photoactivatable
proteins are likely to be a new and generally effective class of tools for manipulating
local protein activities in vivo.