title: Protein kinase C activation decreases peripheral actin network density and increases central nonmuscle myosin II contractility in neuronal growth cones.
abstract: Protein kinase C (PKC) can dramatically alter cell structure and motility via effects on actin filament networks. In neurons, PKC activation has been implicated in repulsive guidance responses and inhibition of axon regeneration; however, the cytoskeletal mechanisms underlying these effects are not well understood. Here we investigate the acute effects of PKC activation on actin network structure and dynamics in large Aplysia neuronal growth cones. We provide evidence of a novel two-tiered mechanism of PKC action: 1) PKC activity enhances myosin II regulatory light chain phosphorylation and C-kinase-potentiated protein phosphatase inhibitor phosphorylation. These effects are correlated with increased contractility in the central cytoplasmic domain. 2) PKC activation results in significant reduction of P-domain actin network density accompanied by Arp2/3 complex delocalization from the leading edge and increased rates of retrograde actin network flow. Our results show that PKC activation strongly affects both actin polymerization and myosin II contractility. This synergistic mode of action is relevant to understanding the pleiotropic reported effects of PKC on neuronal growth and regeneration.
authors: Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06511.
authors: Qing
authors: Q
authors: Yang
authors: Xiao-Feng
authors: XF
authors: Zhang
authors: David
authors: D
authors: Van Goor
authors: Ashleigh P
authors: AP
authors: Dunn
authors: Callen
authors: C
authors: Hyland
authors: Nelson
authors: N
authors: Medeiros
authors: Paul
authors: P
authors: Forscher
mesh_terms: D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism; D000199:Actins / Q000378:metabolism*; D000818:Animals; D001048:Aplysia / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D002465:Cell Movement / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism; D009119:Muscle Contraction / Q000235:genetics / Q000502:physiology; D055495:Neurogenesis / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000235:genetics*; D015398:Signal Transduction
chemical_list: D000199:Actins; D011493:Protein Kinase C; D024507:Nonmuscle Myosin Type IIA
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