title: DCC-dependent phospholipase C signaling in netrin-1-induced neurite elongation.
abstract: Netrins, a family of secreted molecules, play important roles in axon pathfinding during nervous system development. Although phosphatidylinositol signaling has been implicated in this event, how netrin-1 regulates phosphatidylinositol signaling remains poorly understood. Here we provide evidence that netrin-1 stimulates phosphatidylinositol bisphosphate hydrolysis in cortical neurons. This event appears to be mediated by DCC (deleted in colorectal cancer), but not neogenin or Unc5h2. Netrin-1 induces phospholipase Cgamma (PLCgamma) tyrosine phosphorylation. Inhibition of PLC activity attenuates netrin-1-induced cortical neurite outgrowth. These results suggest that netrin-1 regulates phosphatidylinositol turnover and demonstrate a crucial role of PLC signaling in netrin-1-induced neurite elongation.
authors.affiliation: Institute of Molecular Medicine & Genomics and Department of Neurology, Medical College of Georgia, Augusta, Georgia 30809, USA.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xie
authors.forename: Yan
authors.initials: Y
authors.lastname: Hong
authors.forename: Xiao-Yue
authors.initials: XY
authors.lastname: Ma
authors.forename: Xiu-Rong
authors.initials: XR
authors.lastname: Ren
authors.forename: Susan
authors.initials: S
authors.lastname: Ackerman
authors.forename: Lin
authors.initials: L
authors.lastname: Mei
authors.forename: Wen-Cheng
authors.initials: WC
authors.lastname: Xiong
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D000075389:DCC Receptor; D006801:Humans; D051379:Mice; D009414:Nerve Growth Factors / Q000502:physiology*; D000075388:Netrin-1; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000502:physiology*; D010738:Type C Phospholipases / Q000502:physiology*
chemical_list: D000075389:DCC Receptor; C501909:DCC protein, human; C000617351:NTN1 protein, human; D009414:Nerve Growth Factors; C000617353:Ntn1 protein, mouse; C000617354:Ntn1 protein, rat; D018129:Phosphatidylinositol Phosphates; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins; D000075388:Netrin-1; D010738:Type C Phospholipases