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Inhibition of Netrin-Mediated Axon Attraction by a Receptor Protein Tyrosine Phosphatase
Timothy W. Yu,2
Cornelia I. Bargmann,2*
During axon guidance, the ventral guidance of the Caenorhabditiselegans anterior ventral microtubule axon is controlled by twocues, the UNC-6/netrin attractant recognized by the UNC-40/DCCreceptor and the SLT-1/slit repellent recognized by the SAX-3/roboreceptor. We show here that loss-of-function mutations in clr-1enhance netrin-dependent attraction, suppressing ventral guidancedefects in slt-1 mutants. clr-1 encodes a transmembrane receptorprotein tyrosine phosphatase (RPTP) that functions in AVM toinhibit signaling through the DCC family receptor UNC-40 andits effector, UNC-34/enabled. The known effects of other RPTPsin axon guidance could result from modulation of guidance receptorslike 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.