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.
Highlights
Typical mature neurons have a highly polarized structure with a long axon to transmit information and multiple short dendrites to receive information
The pEGFP-Myo10 MF transfected neurons lost typical Tau-1 positive neurites and the longest neurites was decreased to 76.4364.04 mm (Fig. 4C, D and E, n = 250, P,0.001). These results suggested that PH-MyTH4-FERM domains (PHMF) domain was required for axon formation, whereas Myo10 MF domain might competitively inhibit the role of endogenous Myo10
Myo10 is known as a molecular motor, which has been shown to promote filopodia extension under the modulation of PtdIns (3,4,5) P3 in COS 7 kidney carcinoma cells [26]
Summary
Typical mature neurons have a highly polarized structure with a long axon to transmit information and multiple short dendrites to receive information. Selective localizations of molecules determine axon-dendrite differentiation by persistently supplying the elongating axon with growth promoting proteins [3], which is triggered by activation of phosphoinositide 3-kinase (PI3K) and the accumulation of its lipid product of PtdIns (3,4,5) P3 at the tip of future axon [4,5,6,7]. PtdIns (3,4,5) P3, a membrane lipid, is sufficient to stimulate actin cytoskeleton remodeling in coordination with neuronal polarity and axon elongation [8,9,10,11]. Despite the significant progress in identification of numerous actin binding proteins to regulate axon development [13,14,15], the mechanism of axon formation is still not fully understood
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