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.


Logo for

Science 305 (5680): 103-106

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

Inhibition of Netrin-Mediated Axon Attraction by a Receptor Protein Tyrosine Phosphatase

Chieh Chang,1,2 Timothy W. Yu,2 Cornelia I. Bargmann,2* Marc Tessier-Lavigne1*{dagger}

Abstract: During axon guidance, the ventral guidance of the Caenorhabditis elegans anterior ventral microtubule axon is controlled by two cues, the UNC-6/netrin attractant recognized by the UNC-40/DCC receptor and the SLT-1/slit repellent recognized by the SAX-3/robo receptor. We show here that loss-of-function mutations in clr-1 enhance netrin-dependent attraction, suppressing ventral guidance defects in slt-1 mutants. clr-1 encodes a transmembrane receptor protein tyrosine phosphatase (RPTP) that functions in AVM to inhibit signaling through the DCC family receptor UNC-40 and its effector, UNC-34/enabled. The known effects of other RPTPs in axon guidance could result from modulation of guidance receptors like UNC-40/DCC.

1 Department of Biological Sciences, Howard Hughes Medical Institute (HHMI), Stanford University, Stanford, CA 94305, USA.
2 Department of Anatomy and Department of Biochemistry and Biophysics, HHMI, University of California San Francisco (UCSF), San Francisco, CA 94143, USA.

Back to Top

{dagger} Present address: Genentech, Incorporated, 1 DNA Way, South San Francisco, CA 94080, USA.

* To whom correspondence should be addressed. E-mail: cori{at} (C.I.B.); marcH{at} (M.T.L.)

The lin-4 MicroRNA Targets the LIN-14 Transcription Factor to Inhibit Netrin-Mediated Axon Attraction.
Y. Zou, H. Chiu, D. Domenger, C.-F. Chuang, and C. Chang (2012)
Science Signaling 5, ra43
   Abstract »    Full Text »    PDF »
The Chemorepellent Slit3 Promotes Monocyte Migration.
S. B. Geutskens, P. L. Hordijk, and P. B. van Hennik (2010)
J. Immunol. 185, 7691-7698
   Abstract »    Full Text »    PDF »
Protein phosphatase 2A cooperates with the autophagy-related kinase UNC-51 to regulate axon guidance in Caenorhabditis elegans.
K. i. Ogura, T. Okada, S. Mitani, K. Gengyo-Ando, D. L. Baillie, Y. Kohara, and Y. Goshima (2010)
Development 137, 1657-1667
   Abstract »    Full Text »    PDF »
Distinct cellular and molecular mechanisms mediate initial axon development and adult-stage axon regeneration in C. elegans.
C. V. Gabel, F. Antoine, C.-F. Chuang, A. D. T. Samuel, and C. Chang (2008)
Development 135, 1129-1136
   Abstract »    Full Text »    PDF »
Cytoplasmic domain requirements for Frazzled-mediated attractive axon turning at the Drosophila midline.
D. S. Garbe, M. O'Donnell, and G. J. Bashaw (2007)
Development 134, 4325-4334
   Abstract »    Full Text »    PDF »
Dimerization of Protein Tyrosine Phosphatase {sigma} Governs both Ligand Binding and Isoform Specificity.
S. Lee, C. Faux, J. Nixon, D. Alete, J. Chilton, M. Hawadle, and A. W. Stoker (2007)
Mol. Cell. Biol. 27, 1795-1808
   Abstract »    Full Text »    PDF »
Motor Axon Guidance of the Mammalian Trochlear and Phrenic Nerves: Dependence on the Netrin Receptor Unc5c and Modifier Loci.
R. W. Burgess, T. J. Jucius, and S. L. Ackerman (2006)
J. Neurosci. 26, 5756-5766
   Abstract »    Full Text »    PDF »
FAK and Src kinases are required for netrin-induced tyrosine phosphorylation of UNC5.
W. Li, J. Aurandt, C. Jurgensen, Y. Rao, and K.-L. Guan (2006)
J. Cell Sci. 119, 47-55
   Abstract »    Full Text »    PDF »
SRC-1, a non-receptor type of protein tyrosine kinase, controls the direction of cell and growth cone migration in C. elegans.
B. Itoh, T. Hirose, N. Takata, K. Nishiwaki, M. Koga, Y. Ohshima, and M. Okada (2005)
Development 132, 5161-5172
   Abstract »    Full Text »    PDF »
Sensitized genetic backgrounds reveal a role for C. elegans FGF EGL-17 as a repellent for migrating CAN neurons.
T. C. Fleming, F. W. Wolf, and G. Garriga (2005)
Development 132, 4857-4867
   Abstract »    Full Text »    PDF »
SRC-1 Mediates UNC-5 Signaling in Caenorhabditis elegans.
J. Lee, W. Li, and K.-L. Guan (2005)
Mol. Cell. Biol. 25, 6485-6495
   Abstract »    Full Text »    PDF »
The Abelson tyrosine kinase, the Trio GEF and Enabled interact with the Netrin receptor Frazzled in Drosophila.
D. J. Forsthoefel, E. C. Liebl, P. A. Kolodziej, and M. A. Seeger (2005)
Development 132, 1983-1994
   Abstract »    Full Text »    PDF »
Receptor Tyrosine Phosphatases Guide Vertebrate Motor Axons during Development.
L. Stepanek, A. W. Stoker, E. Stoeckli, and J. L. Bixby (2005)
J. Neurosci. 25, 3813-3823
   Abstract »    Full Text »    PDF »
The Conserved Immunoglobulin Domain Controls the Subcellular Localization of the Homophilic Adhesion Receptor Protein-tyrosine Phosphatase {mu}.
R. L. Del Vecchio and N. K. Tonks (2005)
J. Biol. Chem. 280, 1603-1612
   Abstract »    Full Text »    PDF »
mau-2 acts cell-autonomously to guide axonal migrations in Caenorhabditis elegans.
C. Y. Benard, H. Kebir, S. Takagi, and S. Hekimi (2004)
Development 131, 5947-5958
   Abstract »    Full Text »    PDF »
Netrins and neogenin promote myotube formation.
J.-S. Kang, M.-J. Yi, W. Zhang, J. L. Feinleib, F. Cole, and R. S. Krauss (2004)
J. Cell Biol. 167, 493-504
   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