Deleted in Colorectal Cancer (DCC) encodes a netrin receptor.
The guidance of developing axons in the nervous system is mediated partly by diffusible chemoattractants secreted by axonal target cells. Netrins are chemoattractants for commissural axons in the vertebrate spinal cord, but the mechanisms through which they produce their effects are unknown. We show that Deleted in Colorectal Cancer (DCC), a transmembrane protein of the immunoglobulin superfamily, is expressed on spinal commissural axons and possesses netrin-1-binding activity. Moreover, an antibody to DCC selectively blocks the netrin-1-dependent outgrowth of commissural axons in vitro. These results indicate that DCC is a receptor or a component of a receptor that mediates the effects of netrin-1 on commissural axons, and they complement genetic evidence for interactions between DCC and netrin homologs in C. elegans and Drosophila.
Keino-Masu
K
K
Howard Hughes Medical Institute, Department of Anatomy, University of California, San Francisco 94143-0452, USA.
Masu
M
M
Hinck
L
L
Leonardo
E D
ED
Chan
S S
SS
Culotti
J G
JG
Tessier-Lavigne
M
M
D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000502:physiology; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D016147:Genes, Tumor Suppressor; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D011485:Protein Binding; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics*; D011994:Recombinant Proteins; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology / Q000502:physiology; D025521:Tumor Suppressor Proteins
D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D009414:Nerve Growth Factors; C000617354:Ntn1 protein, rat; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C091279:neogenin; D000075388:Netrin-1