Cas family Src homology-3 (SH3)-domain-containing signalling proteins regulate, in non-neuronal cells, actin cytoskeletal dynamics. In neurons,guidance cues and receptors modify cytoskeletal components in growth cones;however, a detailed understanding of the downstream signalling events that influence axon and dendritic pathfinding has remained elusive. On , Jonathan Terman's and Alex Kolodkin's groups now identify a Drosophila Cas(DCas) protein; it is highly expressed in neurons and functions in axon guidance with integrins by regulating the degree of axonal fasciculation. A series of loss-of-function and overexpression experiments in flies shows that DCas interacts in a dose-dependent manner with the α1, α2 andβ1 integrin receptor subunits to regulate motor axon defasciculation and guidance. The loss of DCas or integrin receptors from Drosophilamotor neurons causes axons to grow past, or to stall at, their normal defasciculation point. Integrin-dependent hyperfasciculation defects occur in neurons where DCas is overexpressed. Integrin/DCas-mediated signalling is necessary but not sufficient for axonal defasciculation, thus other components involved in this process await identification.
