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Function of an Axonal Chemoattractant Modulated by Metalloprotease Activity
Michael J. Galko,Marc Tessier-Lavigne*
The axonal chemoattractant netrin-1 guides spinal
commissural axons by activating its receptor DCC (Deleted in ColorectalCancer). We have found that chemical inhibitors of metalloproteasespotentiate netrin-mediated axon outgrowth in vitro. We have alsofound
that DCC is a substrate for metalloprotease-dependent ectodomainshedding, and that the inhibitors block proteolytic processingof DCC
and cause an increase in DCC protein levels on axons withinspinal cord
explants. Thus, potentiation of netrin activity byinhibitors may
result from stabilization of DCC on the axons,and proteolytic activity
may regulate axon migration by controllingthe number of functional
extracellular axon guidance receptors.
Department of Anatomy, Howard Hughes Medical Institute, and
Department of Biochemistry and Biophysics, University of California,
San Francisco, CA 94143, USA.
*
To whom correspondence should be addressed. E-mail:
marctl{at}itsa.ucsf.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
Elena Pasquale (25 August 2000) Science289 (5483), 1308.
[DOI: 10.1126/science.289.5483.1308] |Summary »|Full Text »
REPORTS
Mitsuharu Hattori, Miriam Osterfield, and John G. Flanagan (25 August 2000) Science289 (5483), 1360.
[DOI: 10.1126/science.289.5483.1360] |Abstract »|Full Text »|PDF »
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