title: Metastasis suppressor 1 regulates neurite outgrowth in primary neuron cultures.
abstract: Metastasis suppressor 1 (MTSS1) or missing in metastasis (MIM) is an actin- and membrane-binding protein with tumor suppressor functions. MTSS1 is important for cell morphology, motility, metastasis. The role of MTSS1 in cell morphology has been widely investigated in non-neuronal tissues; however the role of MTSS1 in neurite outgrowth remains unclear. Here we investigated the effect of MTSS1 on neurite outgrowth in primary cerebellar granule and hippocampal neurons of mouse. We found that overexpression of MTSS1 in cerebellar granule neurons significantly enhanced dendrite elaboration but inhibited axon elongation. This phenotype was significantly reduced by deletion of the Wiskott-Aldrich homology 2 (WH2) motif and point mutation in the insulin receptor substrate p53 (IRSp53) and MIM/MTSS1 homology (IMD) domain. Furthermore, inhibition of Rac1 activity or blocking of phosphatidyl inositol phosphates (PIPs) signaling decreased the effect of MTSS1 markedly. In accordance with the over-expression data, knockdown of MTSS1 in cerebellar granule neurons could increase the axon length but decrease the dendrite length and the number of dendrites. In addition, MTSS1 knock down in embryonic hippocampal neurons suppressed neurite branching and reduced dendrite length. Our findings have demonstrated that MTSS1 modulates neuronal morphology, possibly through a Rac1-PIPs signaling pathway.
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Juan
authors.initials: J
authors.lastname: Yu
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Lin
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Liang
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Zijiao
authors.initials: Z
authors.lastname: Zou
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Xinfeng
authors.initials: X
authors.lastname: Zhou
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China.
authors.forename: Meichi
authors.initials: M
authors.lastname: Wang
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China. Electronic address: chenp@hunnu.edu.cn.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: The Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, College of Life Sciences, Hunan Normal University, Changsha 410081, PR China. Electronic address: wangying910000@yahoo.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D048429:Cell Size; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008840:Microfilament Proteins / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D000071446:Neuronal Outgrowth / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000037:antagonists & inhibitors / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: C539986:Baiap2 protein, mouse; D008840:Microfilament Proteins; C473219:Mtss1 protein, mouse; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D018129:Phosphatidylinositol Phosphates; C484602:Rac1 protein, mouse; D020830:rac1 GTP-Binding Protein
keywords: metastasis suppressor 1; neurite outgrowth; neuronal morphology