Metastasis Suppressor 1 Regulate Neuronal Morphology By Affect Neurite Outgrowth

Metastasis suppressor 1(MTSS1),also known as missing in metastasis(MIM)has been implicated in cell morphology,motility,metastasis and development.MTSS1 has been speculated to mediate the cytoskeletal changes and membrane dynamics required for vertebrate neural tube closure.Despite the various studies on the morphological role of MTSS1 in peripheral system,the role of MTSS1 on neurite outgrowth was not very clear.Here the morphological function of MTSS1 on primary neuronal culture was investigated.Over-expression of MTSS1 in cerebellar granular neuron could significantly enhance dendrite elaboration but inhibit axon elongation.However,its Wiskott-Aldrich homology 2 motif deletion mutant and its IRSp53 and MIM(missing in metastases)homology domain mutant have significantly lesser effect than that of wild type.Furthermore,inhibition of Rac1 activity through dominant active Rac or depletion of endogenous phosphatidylinositol 4,5-bisphosphate(PIP2)by inhibitor could decrease the effect of MTSS1 markedly.It suggested that actin dynamics,PIP2 mediated membrane deformation in the neural function of MTSS1.These results suggested that MTSS1 mediated neurite outgrowth requires both the endogenous Rac1 activation and PIP2 signaling.Our study suggest,MTSS1 as a actin binding protein and membrane deformer,modulate the neuronal morphology through small GTPase Rac and phosphatidylinositol signal pathway.