First published online May 30, 2007
Development 134, 1205e (2007)
© The Company of Biologists Limited
Integrins on the Cas(e)
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
p. 2337, 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 
1, 2 and
ß1 integrin receptor subunits to regulate motor axon defasciculation and
guidance. The loss of DCas or integrin receptors from Drosophila
motor 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.
Related articles in Development:
- Crk-associated substrate (Cas) signaling protein functions with integrins to specify axon guidance during development
- Zhiyu Huang, Umar Yazdani, Katherine L. Thompson-Peer, Alex L. Kolodkin, and Jonathan R. Terman
Development 2007 134: 2337-2347.
[Abstract]
[Full Text]
