Document Type
Article
Publication Date
6-15-2012
Publication Title
Journal of Cell Science
Abstract
There is biochemical, imaging and functional evidence that Rho GTPase signaling is a crucial regulator of actin-based structures such as lamellipodia and filopodia. However, although Rho GTPases are believed to serve similar functions in growth cones, the spatiotemporal dynamics of Rho GTPase signaling has not been examined in living growth cones in response to known axon guidance cues. Here we provide the first measurements of Cdc42 activity in living growth cones acutely stimulated with both growth-promoting and growthinhibiting axon-guidance cues. Interestingly, we find that both permissive and repulsive factors can work by modulating Cdc42 activity, but in opposite directions. We find that the growth-promoting factors laminin and BDNF activate Cdc42, whereas the inhibitor Slit2 reduces Cdc42 activity in growth cones. Remarkably, we find that regulation of focal adhesion kinase (FAK) activity is a common upstream modulator of Cdc42 by BDNF, laminin and Slit. These findings suggest that rapid modulation of Cdc42 signaling through FAK by receptor activation underlies changes in growth cone motility in response to permissive and repulsive guidance cues.
Keywords
Axon guidance, Neural development, Pathfinding
Volume
125
Issue
12
First Page
2918
Last Page
2929
DOI
10.1242/jcs.100107
ISSN
00219533
Rights
© 2012. Published by The Company of Biologists Ltd.
Recommended Citation
Myers, Jonathan P.; Robles, Estuardo; Ducharme-Smith, Allison; and Gomez, Timothy M., "Focal Adhesion Kinase Modulates Cdc42 Activity Downstream of Positive and Negative Axon Guidance Cues" (2012). Neuroscience: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/nsc_facpubs/70
Comments
Archived as published. Open access article.