Ral GTPases regulate neurite branching through GAP-43 and the exocyst complex.
Neurite branching is essential for the establishment of appropriate neuronal connections during development and regeneration. We identify the small GTPase Ral as a mediator of neurite branching. Active Ral promotes neurite branching in cortical and sympathetic neurons, whereas Ral inhibition decreases laminin-induced branching. In addition, depletion of endogenous Ral by RNA interference decreases branching in cortical neurons. The two Ral isoforms, RalA and -B, promote branching through distinct pathways, involving the exocyst complex and phospholipase D, respectively. Finally, Ral-dependent branching is mediated by protein kinase C-dependent phosphorylation of 43-kD growth-associated protein, a crucial molecule involved in pathfinding, plasticity, and regeneration. These findings highlight an important role for Ral in the regulation of neuronal morphology.
Lalli
Giovanna
G
Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, England, UK.
Hall
Alan
A
D000199:Actins / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D019922:GAP-43 Protein / Q000502:physiology*; D007797:Laminin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D010739:Phospholipase D / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D017783:Superior Cervical Ganglion / Q000166:cytology; D020725:ral GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D000199:Actins; D019922:GAP-43 Protein; D007797:Laminin; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C082190:Ralb protein, rat; D011493:Protein Kinase C; D010739:Phospholipase D; C492197:Rala protein, rat; D020725:ral GTP-Binding Proteins