DCC-dependent phospholipase C signaling in netrin-1-induced neurite elongation.
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.
Xie
Yi
Y
Institute of Molecular Medicine & Genomics and Department of Neurology, Medical College of Georgia, Augusta, Georgia 30809, USA.
Hong
Yan
Y
Ma
Xiao-Yue
XY
Ren
Xiu-Rong
XR
Ackerman
Susan
S
Mei
Lin
L
Xiong
Wen-Cheng
WC
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*
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