GM130-dependent Control of Cdc42 Activity at the Golgi Regulates Centrosome Organization
GM130-dependent Control of Cdc42 Activity at the Golgi Regulates Centrosome Organization
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DOI：
10.1091/mbc.e08-08-0834
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发表时间：
2009-02-01
影响因子：
3.3
通讯作者：
Suetterlin, Christine
中科院分区：
文献类型：
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作者：
Kodani, Andrew;Kristensen, Irene;Suetterlin, Christine
高尔基体和中心体的物理接近是哺乳动物细胞的独特特征，其功能意义仅知之甚少。在这里，我们表明，先前描述的调节中心体的组织和功能的高尔基体蛋白，GM130，涉及高尔基体相关的复合物组成的GM130，Rho GTdR，Cdc42，和它的鸟嘌呤核苷酸交换因子，Tuba。我们确定了Tuba作为一种新的GM130相互作用蛋白，并表明这种关联控制Tuba介导的高尔基体Cdc42的激活。阻断Tuba或Cdc42的活性可复制异常的、无功能的中心体的GM130耗竭表型。组成型活性Cdc42的表达绕过了中心体调节中对GM130的要求，表明Cdc42在GM130的下游起作用。我们的研究表明，Cdc42在控制中心体组织在未受刺激的细胞除了其已知的功能作为一个调节器的中心体在受刺激的细胞中的重新定位有一个新的作用。这第一次描述的高尔基体和间期中心体之间的调节途径，补充了已知的作用，高尔基体蛋白在控制纺锤体的形成在有丝分裂过程中，并可能提供一个解释的pericentriolar位置哺乳动物高尔基体在间期。
The physical proximity of the Golgi apparatus and the centrosome is a unique feature of mammalian cells whose functional significance is only poorly understood. Here, we demonstrate that the previously described regulation of centrosome organization and function by the Golgi protein, GM130, involves a Golgi-associated complex consisting of GM130, the Rho GTPase, Cdc42, and its guanine nucleotide exchange factor, Tuba. We identified Tuba as a novel GM130-interacting protein and showed that this association controls Tuba-mediated activation of Cdc42 at the Golgi apparatus. Blocking either Tuba or Cdc42 activity reproduced the GM130 depletion phenotype of aberrant, nonfunctional centrosomes. Expression of constitutively active Cdc42 bypassed the requirement for GM130 in centrosome regulation, indicating that Cdc42 functions downstream of GM130. Our studies demonstrate that Cdc42 has a novel role in controlling centrosome organization in unstimulated cells in addition to its known function as a regulator of centrosome reorientation in stimulated cells. This first description of a regulatory pathway between the Golgi apparatus and the interphase centrosome that complements the known role of Golgi proteins in controlling spindle formation during mitosis and may provide an explanation for the pericentriolar position of the mammalian Golgi apparatus during interphase.