The Actin Cytoskeleton Is Involved in Glial Cell Line-Derived Neurotrophic Factor (GDNF)-Induced Ret Translocation into Lipid Rafts in Dopaminergic Neuronal Cells.
The Actin Cytoskeleton Is Involved in Glial Cell Line-Derived Neurotrophic Factor (GDNF)-Induced Ret Translocation into Lipid Rafts in Dopaminergic Neuronal Cells.
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肌动蛋白细胞骨架参与胶质细胞系衍生神经营养因子 (GDNF) 诱导的多巴胺能神经细胞中的 RET 易位至脂筏中
DOI：
10.3390/ijms18091922
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发表时间：
2017-09-07
影响因子：
5.6
通讯作者：
Gao D
中科院分区：
文献类型：
--
作者：
Li L;Song H;Mu P;Xu M;Liu C;Wang Y;Qin Y;Sun S;Gao J;Wang T;Gao D
胶质细胞源性神经营养因子（GDNF）是一种潜在的治疗帕金森病（PD）的因子，其生物学作用是通过Ret受体酪氨酸激酶实现的。Ret在脂筏中的再分布对Ret信号转导有重要影响，但Ret转位的机制尚不清楚。本研究的目的是进一步探讨GDNF的信号转导机制，并确定肌动蛋白细胞骨架是否参与GDNF诱导的Ret向脂筏的转位。在MN 9D多巴胺能神经元细胞中，我们使用密度梯度离心和免疫荧光共聚焦显微镜来分离和可视化脂筏，免疫共沉淀来分析蛋白质-蛋白质相互作用，以及latrunculin B（Lat B）和jasplakin（Jas）来分别破坏和增强肌动蛋白细胞骨架的聚合。结果表明，GDNF处理后，Ret移位到脂筏中，并与肌动蛋白发生免疫共沉淀。Lat B或Jas处理后，GDNF诱导的Ret-F-actin结合分别被削弱或增强，Ret转位到脂筏的水平相应被抑制或增强。这些数据表明，肌动蛋白聚合和细胞骨架重塑是不可或缺的GDNF诱导的细胞信号在多巴胺能细胞，并定义了一个新的作用，肌动蛋白细胞骨架在促进Ret重新分配到脂筏。
Glial cell line-derived neurotrophic factor (GDNF), a potential therapeutic factor for Parkinson’s disease (PD), exerts its biological effects through the Ret receptor tyrosine kinase. The redistribution of Ret into lipid rafts substantially influences Ret signaling, but the mechanisms underlying Ret translocation remain unclear. The purpose of our study was to further explore the signaling mechanisms of GDNF and to determine whether the actin cytoskeleton is involved in the GDNF-induced Ret translocation into lipid rafts. In MN9D dopaminergic neuronal cells, we used density gradient centrifugation and immunofluorescence confocal microscopy to separate and visualize lipid rafts, co-immunoprecipitation to analyze protein-protein interactions, and latrunculin B (Lat B) and jasplakinolide (Jas) to disrupt and enhance the polymerization of the actin cytoskeleton, respectively. The results showed that Ret translocated into lipid rafts and coimmunoprecipitated with actin in response to GDNF treatment. After Lat B or Jas treatment, the Ret–F-actin association induced by GDNF was impaired or enhanced respectively and then the levels of Ret translocated into lipid rafts were correspondingly inhibited or promoted. These data indicate that actin polymerization and cytoskeletal remodeling are integral to GDNF-induced cell signaling in dopaminergic cells and define a new role of the actin cytoskeleton in promoting Ret redistribution into lipid rafts.
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影响因子：
3.3
作者：
Migliore, M. M.;Ortiz, R.;Waszczak, B. L.
通讯作者：
Waszczak, B. L.
影响因子：
56.9
作者：
LIN, LFH;DOHERTY, DH;COLLINS, F
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COLLINS, F
影响因子：
7.2
作者：
Simons, Kai;Sampaio, Julio L.
通讯作者：
Sampaio, Julio L.
影响因子：
4.8
作者：
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通讯作者：
Perlmann, T
影响因子：
3.7
作者：
Rodgers, W;Zavzavadjian, J
通讯作者：
Zavzavadjian, J