METASTASIS SUPPRESSOR 1 REGULATES NEURITE OUTGROWTH IN PRIMARY NEURON CULTURES

METASTASIS SUPPRESSOR 1 REGULATES NEURITE OUTGROWTH IN PRIMARY NEURON CULTURES
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转移抑制因子 1 调节原代神经元培养物中的神经突生长

DOI:
10.1016/j.neuroscience.2016.07.002
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发表时间:
2016-10
期刊:
影响因子:
3.3
通讯作者:
Wang Ying
Wang Ying
中科院分区:
医学3区
文献类型:
--
作者:
Yu Juan;Lin Shuyun;Liang Mei Wang Lijun;Zou Zijiao;Zhou Xinfeng;Wang Meichi;Chen Ping;Wang Ying

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转移抑制蛋白 1 (MTSS1) 或转移缺失 (MIM) 是一种具有肿瘤抑制功能的肌动蛋白和膜结合蛋白。 MTSS1 对于细胞形态、运动、转移很重要。 MTSS1 在细胞形态中的作用已在非神经元组织中得到广泛研究;然而,MTSS1 在神经突生长中的作用仍不清楚。在这里,我们研究了 MTSS1 对小鼠初级小脑颗粒和海马神经元神经突生长的影响。我们发现小脑颗粒神经元中 MTSS1 的过度表达显着增强了树突的精细化,但抑制了轴突的伸长。通过删除 Wiskott-Aldrich 同源 2 (WH2) 基序以及胰岛素受体底物 p53 (IRSp53) 和 MIM/MTSS1 同源 (IMD) 结构域中的点突变,该表型显着降低。此外,抑制 Rac1 活性或阻断磷脂酰肌醇磷酸 (PIPs) 信号传导会显着降低 MTSS1 的作用。根据过表达数据,小脑颗粒神经元中MTSS1的敲低可以增加轴突长度,但减少树突长度和树突数量。此外,胚胎海马神经元中的 MTSS1 敲除抑制了神经突分支并减少了树突长度。我们的研究结果表明,MTSS1 可能通过 Rac1-PIPs 信号通路调节神经元形态。
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.
DOI: 10.3389/fnsyn.2013.00004
发表时间: 2013
影响因子: 3.7
作者:
Vadodaria KC;Jessberger S
通讯作者: Jessberger S
正常和转化的小脑细胞中转移1(MTSS1)的发育表达和分化相关的神经元特异性剪接。
DOI: 10.1186/1471-213x-7-111
发表时间: 2007-10-09
影响因子: --
作者:
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DOI: 10.4161/sgtp.29469
发表时间: 2014-01-01
期刊: Small GTPases
影响因子: --
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发表时间: 2011-04-15
影响因子: 4
作者:
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通讯作者: Lappalainen, Pekka
DOI: 10.1007/978-0-387-76715-4_1
发表时间: 2007-01-01
期刊: AXON GROWTH AND GUIDANCE
影响因子: --
作者:
Bouquet, Celine;Nothias, Fatiha
通讯作者: Nothias, Fatiha