Department of Cell Biology and Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA.
Axon guidance requires the integration of diverse guidance signals presented by numerous extracellular cues and cell-cell interactions. The molecular mechanisms that interpret these signals involve networks of intracellular signaling proteins that coordinate a variety of responses to the environment, including remodeling and assembly of the actin cytoskeleton. Although it has been clear for some time that Rho family GTPases play a central role in the orchestration of cytoskeletal assembly, our understanding of the components that regulate these important molecules is far more primitive. Recent functional studies of the Trio family of guanine-nucleotide-exchange factors reveal that Trio proteins play a vital role in neuronal cell migration and axon guidance. Although the molecular analysis of Trio proteins is still in its infancy, accumulated evidence suggests that Trio proteins function as integrators of multiple upstream inputs and as activators of multiple downstream pathways. Future studies of these mechanisms promise to yield insights not only into neural development but also into the ongoing function and remodeling of the adult nervous system.