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Science 291 (5510): 1976-1982

Copyright © 2001 by the American Association for the Advancement of Science

Binding of DCC by Netrin-1 to Mediate Axon Guidance Independent of Adenosine A2B Receptor Activation

Elke Stein,1 Yimin Zou,1* Mu-ming Poo,2 Marc Tessier-Lavigne1dagger

Netrins stimulate and orient axon growth through a mechanism requiring receptors of the DCC family. It has been unclear, however, whether DCC proteins are involved directly in signaling or are mere accessory proteins in a receptor complex. Further, although netrins bind cells expressing DCC, direct binding to DCC has not been demonstrated. Here we show that netrin-1 binds DCC and that the DCC cytoplasmic domain fused to a heterologous receptor ectodomain can mediate guidance through a mechanism involving derepression of cytoplasmic domain multimerization. Activation of the adenosine A2B receptor, proposed to contribute to netrin effects on axons, is not required for rat commissural axon outgrowth or Xenopus spinal axon attraction to netrin-1. Thus, DCC plays a central role in netrin signaling of axon growth and guidance independent of A2B receptor activation.

1 Departments of Anatomy and of Biochemistry and Biophysics, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143-0452, USA.
2 Department of Molecular and Cell Biology, University of California, Berkeley, CA 14720-3200, USA.
*   Present address: Department of Neurobiology, Pharmacology and Physiology, University of Chicago, J. F. Knapp Research Center, Room 216, 924 East 57 Street, Chicago, IL 60637, USA.

dagger    To whom correspondence should be addressed. E-mail: marctl{at}itsa.ucsf.edu

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