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Science 20 February 2004:
Vol. 303. no. 5661, pp. 1204 - 1207
DOI: 10.1126/science.1092121
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Reports

Nervy Links Protein Kinase A to Plexin-Mediated Semaphorin Repulsion

Jonathan R. Terman and Alex L. Kolodkin*

Cyclic nucleotides regulate axonal responses to a number of guidance cues through unknown molecular events. We report here that Drosophila nervy, a member of the myeloid translocation gene family of A kinase anchoring proteins (AKAPs), regulates repulsive axon guidance by linking the cyclic adenosine monophosphate (cAMP)–dependent protein kinase (PKA) to the Semaphorin 1a (Sema-1a) receptor Plexin A (PlexA). Nervy and PKA antagonize Sema-1a-PlexA–mediated repulsion, and the AKAP binding region of Nervy is critical for this effect. Thus, Nervy couples cAMP-PKA signaling to PlexA to regulate Sema-1a–mediated axonal repulsion, revealing a simple molecular mechanism that allows growing axons to integrate inputs from multiple guidance cues.

Department of Neuroscience, Johns Hopkins University School of Medicine, 1001 PCTB/725 North Wolfe Street, Baltimore, MD 21205, USA.

* To whom correspondence should be addressed. E-mail: kolodkin{at}jhmi.edu

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