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Science 303 (5661): 1204-1207

Copyright © 2004 by the American Association for the Advancement of Science

Nervy Links Protein Kinase A to Plexin-Mediated Semaphorin Repulsion

Jonathan R. Terman, and Alex L. Kolodkin*

Abstract: 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}

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