Guo W, Tamanoi F, Novick P
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06520-8002, USA.
Nat Cell Biol. 2001 Apr;3(4):353-60. doi: 10.1038/35070029.
Spatial regulation of membrane traffic is fundamental to many biological processes, including epithelial cell polarization and neuronal synaptogenesis. The multiprotein exocyst complex is localized to sites of polarized exocytosis, and is required for vesicle targeting and docking at specific domains of the plasma membrane. One component of the complex, Sec3, is thought to be a spatial landmark for polarized exocytosis. We have searched for proteins that regulate the polarized localization of the exocyst in the budding yeast Saccharomyces cerevisiae. Here we report that certain rho1 mutant alleles specifically affect the localization of the exocyst proteins. Sec3 interacts directly with Rho1 in its GTP-bound form, and functional Rho1 is needed both to establish and to maintain the polarized localization of Sec3. Sec3 is not the only mediator of the effect of Rho1 on the exocyst, because some members of the complex are correctly targeted independently of the interaction between Rho1 and Sec3. These results reveal the action of parallel pathways for the polarized localization of the exocytic machinery, both of which are under the control of Rho1, a master regulator of cell polarity.
膜泡运输的空间调控是许多生物学过程的基础，包括上皮细胞极化和神经元突触形成。多蛋白外泌体复合物定位于极化胞吐作用的位点，是囊泡靶向和停靠在质膜特定结构域所必需的。该复合物的一个组分Sec3被认为是极化胞吐作用的空间标志物。我们在出芽酵母酿酒酵母中寻找调节外泌体极化定位的蛋白质。在此我们报告，某些rho1突变等位基因特异性地影响外泌体蛋白的定位。Sec3以其GTP结合形式直接与Rho1相互作用，功能性的Rho1对于建立和维持Sec3的极化定位都是必需的。Sec3不是Rho1对外泌体作用的唯一介导因子，因为该复合物的一些成员能独立于Rho1与Sec3之间的相互作用而正确靶向。这些结果揭示了外排机制极化定位的平行途径的作用，这两条途径均受细胞极性的主要调节因子Rho1的控制。
