Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

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}jhmi.edu


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Semaphorin Signaling Meets Rap.
J. L. Bos and W.-J. Pannekoek (2012)
Science Signaling 5, pe6
   Abstract »    Full Text »    PDF »
Spatial and temporal second messenger codes for growth cone turning.
X. Nicol, K. P. Hong, and N. C. Spitzer (2011)
PNAS 108, 13776-13781
   Abstract »    Full Text »    PDF »
Drosophila Mmp2 Regulates the Matrix Molecule Faulty Attraction (Frac) to Promote Motor Axon Targeting in Drosophila.
C. M. Miller, N. Liu, A. Page-McCaw, and H. T. Broihier (2011)
J. Neurosci. 31, 5335-5347
   Abstract »    Full Text »    PDF »
Plexin A-Semaphorin-1a Reverse Signaling Regulates Photoreceptor Axon Guidance in Drosophila.
L. Yu, Y. Zhou, S. Cheng, and Y. Rao (2010)
J. Neurosci. 30, 12151-12156
   Abstract »    Full Text »    PDF »
Matrix metalloproteinases promote motor axon fasciculation in the Drosophila embryo.
C. M. Miller, A. Page-McCaw, and H. T. Broihier (2008)
Development 135, 95-109
   Abstract »    Full Text »    PDF »
The AKAP Yu is required for olfactory long-term memory formation in Drosophila.
Y. Lu, Y.-S. Lu, Y. Shuai, C. Feng, T. Tully, Z. Xie, Y. Zhong, and H.-M. Zhou (2007)
PNAS 104, 13792-13797
   Abstract »    Full Text »    PDF »
Spatial targeting of type II protein kinase A to filopodia mediates the regulation of growth cone guidance by cAMP.
J. Han, L. Han, P. Tiwari, Z. Wen, and J. Q. Zheng (2007)
J. Cell Biol. 176, 101-111
   Abstract »    Full Text »    PDF »
Imaging of cAMP Levels and Protein Kinase A Activity Reveals That Retinal Waves Drive Oscillations in Second-Messenger Cascades.
T. A. Dunn, C.-T. Wang, M. A. Colicos, M. Zaccolo, L. M. DiPilato, J. Zhang, R. Y. Tsien, and M. B. Feller (2006)
J. Neurosci. 26, 12807-12815
   Abstract »    Full Text »    PDF »
Axon Pruning and Synaptic Development: How Are They per-Plexin?.
K. E. Waimey and H.-J. Cheng (2006)
Neuroscientist 12, 398-409
   Abstract »    PDF »
Semaphorins in axon regeneration: developmental guidance molecules gone wrong?.
R. J. Pasterkamp and J. Verhaagen (2006)
Phil Trans R Soc B 361, 1499-1511
   Abstract »    Full Text »    PDF »
Semaphorin-1a Functions as a Guidance Receptor in the Drosophila Visual System.
P. Cafferty, L. Yu, H. Long, and Y. Rao (2006)
J. Neurosci. 26, 3999-4003
   Abstract »    Full Text »    PDF »
Genome-wide analyses identify transcription factors required for proper morphogenesis of Drosophila sensory neuron dendrites.
J. Z. Parrish, M. D. Kim, L. Y. Jan, and Y. N. Jan (2006)
Genes & Dev. 20, 820-835
   Abstract »    Full Text »    PDF »
De Novo GMP Synthesis Is Required for Axon Guidance in Drosophila.
H. Long, S. Cameron, L. Yu, and Y. Rao (2006)
Genetics 172, 1633-1642
   Abstract »    Full Text »    PDF »
cAMP Differentially Regulates Axonal and Dendritic Development of Dentate Granule Cells.
R. X. Yamada, N. Matsuki, and Y. Ikegaya (2005)
J. Biol. Chem. 280, 38020-38028
   Abstract »    Full Text »    PDF »
Comment on "Nervy Links Protein Kinase A to Plexin-Mediated Semaphorin Repulsion".
R. J. Ice, J. Wildonger, R. S. Mann, and S. W. Hiebert (2005)
Science 309, 558b
   Full Text »    PDF »
Response to Comment on "Nervy Links Protein Kinase A to Plexin-Mediated Semaphorin Repulsion".
J. R. Terman and A. L. Kolodkin (2005)
Science 309, 558c
   Full Text »    PDF »
2004: Signaling Breakthroughs of the Year.
E. M. Adler, N. R. Gough, and L. B. Ray (2005)
Sci. STKE 2005, eg1
   Abstract »    Full Text »    PDF »
The Neurotransmitter Glutamate Reduces Axonal Responsiveness to Multiple Repellents through the Activation of Metabotropic Glutamate Receptor 1.
T. A. Kreibich, S. H. Chalasani, and J. A. Raper (2004)
J. Neurosci. 24, 7085-7095
   Abstract »    Full Text »    PDF »
The Drosophila Receptor Guanylyl Cyclase Gyc76C Is Required for Semaphorin-1a-Plexin A-Mediated Axonal Repulsion.
J. C. Ayoob, H.-H. Yu, J. R. Terman, and A. L. Kolodkin (2004)
J. Neurosci. 24, 6639-6649
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882