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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.

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

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

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