The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1.
Netrins are a family of secreted proteins that function as tropic cues directing cell and axon migration during neural development. We show that the netrin-1 receptor, deleted in colorectal cancer (DCC), is present at filopodia tips in growth cones of embryonic rat spinal commissural neurons. To further investigate DCC function, we characterized the expression of netrins and netrin receptors in HEK293T cells and NG108-15 cells and found that they express netrin-1 but do not express DCC. Ectopic expression of DCC produced a netrin-1-dependent increase in the number of filopodia and in cell surface area. Coexpression of DCC and dominant negative Cdc42 or dominant negative Rac1 blocked the increase in filopodia number and cell surface area, respectively. Furthermore, addition of netrin-1 to cells expressing DCC caused a persistent activation of Cdc42 and Rac1. These findings suggest that netrin-1, via DCC, influences cellular motility by regulating actin-based membrane extension through the activation of Cdc42 and Rac1.
Shekarabi
Masoud
M
Centre for Neuronal Survival, McGill University, Montreal, Quebec, H3A 2B4, Canada.
Kennedy
Timothy E
TE
D000199:Actins / Q000378:metabolism; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D000075389:DCC Receptor; D005910:Glioma; D020439:Growth Cones / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000166:cytology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology; D000075386:Netrin Receptors; D000075388:Netrin-1; D009447:Neuroblastoma; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011554:Pseudopodia / Q000502:physiology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*; D020830:rac1 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D015815:Cell Adhesion Molecules; D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; D000075386:Netrin Receptors; C000617354:Ntn1 protein, rat; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein