PMID- 10958786 OWN - NLM STAT- MEDLINE DCOM- 20000907 LR - 20190619 IS - 0036-8075 (Print) IS - 0036-8075 (Linking) VI - 289 IP - 5483 DP - 2000 Aug 25 TI - Function of an axonal chemoattractant modulated by metalloprotease activity. PG - 1365-7 AB - The axonal chemoattractant netrin-1 guides spinal commissural axons by activating its receptor DCC (Deleted in Colorectal Cancer). We have found that chemical inhibitors of metalloproteases potentiate netrin-mediated axon outgrowth in vitro. We have also found that DCC is a substrate for metalloprotease-dependent ectodomain shedding, and that the inhibitors block proteolytic processing of DCC and cause an increase in DCC protein levels on axons within spinal cord explants. Thus, potentiation of netrin activity by inhibitors may result from stabilization of DCC on the axons, and proteolytic activity may regulate axon migration by controlling the number of functional extracellular axon guidance receptors. FAU - Galko, M J AU - Galko MJ AD - Department of Anatomy, Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA. FAU - Tessier-Lavigne, M AU - Tessier-Lavigne M LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Science JT - Science (New York, N.Y.) JID - 0404511 RN - 0 (Cell Adhesion Molecules) RN - 0 (Nerve Growth Factors) RN - 0 (Ntn1 protein, rat) RN - 0 (Phenanthrolines) RN - 0 (Protease Inhibitors) RN - 0 (Tumor Suppressor Proteins) RN - 158651-98-0 (Netrin-1) RN - EC 3.4.24.- (Metalloendopeptidases) RN - W4X6ZO7939 (1,10-phenanthroline) SB - IM CIN - Science. 2000 Aug 25;289(5483):1308-10. PMID: 10979856 MH - Animals MH - Axons/*physiology MH - CHO Cells MH - Cell Adhesion Molecules/chemistry/*metabolism MH - Cricetinae MH - Culture Techniques MH - Growth Cones/physiology MH - Metalloendopeptidases/antagonists & inhibitors/*metabolism MH - Nerve Growth Factors/*metabolism MH - Netrin-1 MH - Phenanthrolines/pharmacology MH - Protease Inhibitors/pharmacology MH - Rats MH - Spinal Cord/*cytology/*enzymology/metabolism MH - *Tumor Suppressor Proteins EDAT- 2000/08/26 11:00 MHDA- 2000/09/09 11:01 CRDT- 2000/08/26 11:00 PHST- 2000/08/26 11:00 [pubmed] PHST- 2000/09/09 11:01 [medline] PHST- 2000/08/26 11:00 [entrez] AID - 8774 [pii] AID - 10.1126/science.289.5483.1365 [doi] PST - ppublish SO - Science. 2000 Aug 25;289(5483):1365-7. doi: 10.1126/science.289.5483.1365.