RhoA/ROCK regulation of neuritogenesis via profilin IIa-mediated control of actin stability.
Neuritogenesis, the first step of neuronal differentiation, takes place as nascent neurites bud from the immediate postmitotic neuronal soma. Little is known about the mechanisms underlying the dramatic morphological changes that characterize this event. Here, we show that RhoA activity plays a decisive role during neuritogenesis of cultured hippocampal neurons by recruiting and activating its specific kinase ROCK, which, in turn, complexes with profilin IIa. We establish that this previously uncharacterized brain-specific actin-binding protein controls neurite sprouting by modifying actin stability, a function regulated by ROCK-mediated phosphorylation. Furthermore, we determine that this novel cascade is switched on or off by physiological stimuli. We propose that RhoA/ROCK/PIIa-mediated regulation of actin stability, shown to be essential for neuritogenesis, may constitute a central mechanism throughout neuronal differentiation.
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D048429:Cell Size / Q000502:physiology; D002478:Cells, Cultured; D003285:Contractile Proteins; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology; D016501:Neurites / Q000201:enzymology; D009474:Neurons / Q000201:enzymology* / Q000648:ultrastructure; D051304:Profilins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
D003285:Contractile Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; D009414:Nerve Growth Factors; C495741:PFN2 protein, human; C495743:Pfn2 protein, rat; D051304:Profilins; D017346:Protein Serine-Threonine Kinases; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein