title: PtdIns (3,4,5) P3 recruitment of Myo10 is essential for axon development.
abstract: Myosin X (Myo10) with pleckstrin homology (PH) domains is a motor protein acting in filopodium initiation and extension. However, its potential role has not been fully understood, especially in neuronal development. In the present study the preferential accumulation of Myo10 in axon tips has been revealed in primary culture of hippocampal neurons with the aid of immunofluorescence from anti-Myo10 antibody in combination with anti-Tuj1 antibody as specific marker. Knocking down Myo10 gene transcription impaired outgrowth of axon with loss of Tau-1-positive phenotype. Interestingly, inhibition of actin polymerization by cytochalasin D rescued the defect of axon outgrowth. Furthermore, ectopic expression of Myo10 with enhanced green fluorescence protein (EGFP) labeled Myo10 mutants induced multiple axon-like neurites in a motor-independent way. Mechanism studies demonstrated that the recruitment of Myo10 through its PH domain to phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5) P3) was essential for axon formation. In addition, in vivo studies confirmed that Myo10 was required for neuronal morphological transition during radial neuronal migration in the developmental neocortex.
authors.affiliation: Key Laboratory of Molecular Epigenetics of Ministry of Education, Institute of Cytology and Genetics, Northeast Normal University, Changchun, China.
authors.forename: Huali
authors.initials: H
authors.lastname: Yu
authors.forename: Nannan
authors.initials: N
authors.lastname: Wang
authors.forename: Xingda
authors.initials: X
authors.lastname: Ju
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.forename: Dong
authors.initials: D
authors.lastname: Sun
authors.forename: Mingming
authors.initials: M
authors.lastname: Lai
authors.forename: Lei
authors.initials: L
authors.lastname: Cui
authors.forename: Muhammad Abid
authors.initials: MA
authors.lastname: Sheikh
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Xingzhi
authors.initials: X
authors.lastname: Wang
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009218:Myosins / Q000096:biosynthesis* / Q000235:genetics; D019579:Neocortex / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*
chemical_list: D000199:Actins; D000911:Antibodies, Monoclonal; C409064:Myo10 protein, mouse; D009419:Nerve Tissue Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D018129:Phosphatidylinositol Phosphates; C060974:phosphatidylinositol 3,4,5-triphosphate; C085348:tau-1 monoclonal antibody; D015638:Cytochalasin D; D009218:Myosins