Structure-Function Analysis of Core STRIPAK Proteins A SIGNALING COMPLEX IMPLICATED IN GOLGI POLARIZATION
Structure-Function Analysis of Core STRIPAK Proteins A SIGNALING COMPLEX IMPLICATED IN GOLGI POLARIZATION
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DOI：
10.1074/jbc.m110.214486
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发表时间：
2011-07-15
影响因子：
4.8
通讯作者：
Gingras, Anne-Claude
中科院分区：
文献类型：
--
作者：
Kean, Michelle J.;Ceccarelli, Derek F.;Gingras, Anne-Claude
脑海绵状血管畸形（CCM）是脑毛细血管结构的改变，可导致神经功能缺损、癫痫发作或中风。我们最近证明，CCM 3，一种在家族性CCM中突变的蛋白质，主要存在于STRIPAK复合物（纹状体相互作用的磷酸酶和激酶）中。沿着CCM 3，STRIPAK含有Ser/Thr磷酸酶PP 2A。PP 2A全酶由一个核心催化亚基沿着与可变的支架和调节亚基组成。在STRIPAK中，纹状体蛋白家族成员充当PP 2A调节亚基。STRIPAK还包含称为GCKIII蛋白的Sterile 20激酶亚家族的所有三个成员（MST 4、STK 24和STK 25）。在这里，我们报告说，纹状体蛋白和CCM 3桥磷酸酶和激酶组成的STRIPAK和地图上的相互作用区域的每种蛋白质。我们发现，纹状体蛋白和CCM 3调节高尔基体定位MST 4以相反的方式。与先前描述的MST 4和CCM 3在高尔基体定位中的功能一致，CCM 3或纹状体蛋白的缺失也以相反的方式影响高尔基体极化。我们建议，STRIPAK调节MST 4定位在高尔基体和细胞质之间的平衡，以控制高尔基体定位。
Cerebral cavernous malformations (CCMs) are alterations in brain capillary architecture that can result in neurological deficits, seizures, or stroke. We recently demonstrated that CCM3, a protein mutated in familial CCMs, resides predominantly within the STRIPAK complex (striatin interacting phosphatase and kinase). Along with CCM3, STRIPAK contains the Ser/Thr phosphatase PP2A. The PP2A holoenzyme consists of a core catalytic subunit along with variable scaffolding and regulatory subunits. Within STRIPAK, striatin family members act as PP2A regulatory subunits. STRIPAK also contains all three members of a subfamily of Sterile 20 kinases called the GCKIII proteins (MST4, STK24, and STK25). Here, we report that striatins and CCM3 bridge the phosphatase and kinase components of STRIPAK and map the interacting regions on each protein. We show that striatins and CCM3 regulate the Golgi localization of MST4 in an opposite manner. Consistent with a previously described function for MST4 and CCM3 in Golgi positioning, depletion of CCM3 or striatins affects Golgi polarization, also in an opposite manner. We propose that STRIPAK regulates the balance between MST4 localization at the Golgi and in the cytosol to control Golgi positioning.