Src kinase regulates the integrity and function of the Golgi apparatus via activation of dynamin 2
Src kinase regulates the integrity and function of the Golgi apparatus via activation of dynamin 2
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DOI：
10.1073/pnas.0915123107
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发表时间：
2010-03-30
影响因子：
11.1
通讯作者：
McNiven, Mark A.
中科院分区：
文献类型：
--
作者：
Weller, Shaun G.;Capitani, Mirco;McNiven, Mark A.
高尔基体的大小和完整性是通过使用各种不同的信号和细胞骨架蛋白对膜交通的严格控制来维持的。我们最近观察到c-Src的激活对高尔基体结构有深远的影响，导致多种细胞类型的池急剧起泡。由于大GTPase动力蛋白（Dyn2）与分泌过程中的高尔基体囊泡有关，我们测试了通过表达Dyn2K44A突变体或敲低siRNA来抑制Dyn2活性是否可以减弱src诱导的高尔基体断裂。事实上，这些扰动减弱了片段化，并且不能被Src激酶磷酸化的Dyn2Y(231/597) F突变蛋白的表达具有类似的效果。最后，我们发现在VSV-G蛋白通过TGN的运输过程中，Dyn2被显著磷酸化，而Dyn2Y(231/597) F突变体的表达显著减少了新生蛋白从TGN的出口。这些发现表明，Src激酶激活Dyn2可调节分泌过程中的高尔基体完整性和囊泡形成。
The size and integrity of the Golgi apparatus is maintained via a tightly controlled regulation of membrane traffic using a variety of different signaling and cytoskeletal proteins. We have recently observed that activation of c-Src has profound effects on Golgi structure, leading to dramatically vesiculated cisternae in a variety of cell types. As the large GTPase dynamin (Dyn2) has been implicated in Golgi vesiculation during secretion, we tested whether inhibiting Dyn2 activity by expression of a Dyn2K44A mutant or siRNA knockdown could attenuate active Src-induced Golgi fragmentation. Indeed, these perturbations attenuated fragmentation, and expression of a Dyn2Y(231/597) F mutant protein that cannot be phosphorylated by Src kinase had a similar effect. Finally, we find that Dyn2 is markedly phosphorylated during the transit of VSV-G protein through the TGN whereas expression of the Dyn2Y(231/597) F mutant significantly reduces exit of the nascent protein from this compartment. These findings demonstrate that activation of Dyn2 by Src kinase regulates Golgi integrity and vesiculation during the secretory process.