title: Ezrin mediates neuritogenesis via down-regulation of RhoA activity in cultured cortical neurons.
abstract: Neuronal morphogenesis is implicated in neuronal function and development with rearrangement of cytoskeletal organization. Ezrin, a member of Ezrin/Radixin/Moesin (ERM) proteins links between membrane proteins and actin cytoskeleton, and contributes to maintenance of cellular function and morphology. In cultured hippocampal neurons, suppression of both radixin and moesin showed deficits in growth cone morphology and neurite extensions. Down-regulation of ezrin using siRNA caused impairment of netrin-1-induced axon outgrowth in cultured cortical neurons. However, roles of ezrin in the neuronal morphogenesis of the cultured neurons have been poorly understood. In this report, we performed detailed studies on the roles of ezrin in the cultured cortical neurons prepared from the ezrin knockdown (Vil2(kd/kd)) mice embryo that showed a very small amount of ezrin expression compared with the wild-type (Vil2(+/+)) neurons. Ezrin was mainly expressed in cell body in the cultured cortical neurons. We demonstrated that the cultured cortical neurons prepared from the Vil2(kd/kd) mice embryo exhibited impairment of neuritogenesis. Moreover, we observed increased RhoA activity and phosphorylation of myosin light chain 2 (MLC2), as a downstream effector of RhoA in the Vil2(kd/kd) neurons. In addition, inhibition of Rho kinase and myosin II rescued the impairment of neuritogenesis in the Vil2(kd/kd) neurons. These data altogether suggest a novel role of ezrin in the neuritogenesis of the cultured cortical neurons through down-regulation of RhoA activity.
authors.affiliation: Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Matsumoto
authors.affiliation: Laboratory of Medical Therapeutics and Molecular Therapeutics, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Inden
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Hatano
authors.affiliation: Laboratory of Biological Science, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Sachiko
authors.initials: S
authors.lastname: Tsukita
authors.affiliation: Department of Molecular Physiology, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Asano
mesh_terms: D000577:Amides / Q000494:pharmacology; D000818:Animals; D024722:Cardiac Myosins / Q000037:antagonists & inhibitors / Q000378:metabolism; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000037:antagonists & inhibitors / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport; D017966:Pyramidal Cells / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000577:Amides; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D018994:Myosin Light Chains; D011725:Pyridines; C107184:myosin light chain 2; C108830:Y 27632; C071776:radixin; D024722:Cardiac Myosins; D020742:rhoA GTP-Binding Protein