Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules.
Epithelial polarity requires septin coupling of vesicle transport to polyglutamylated microtubules.
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DOI：
10.1083/jcb.200710039
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发表时间：
2008-01-28
期刊：
影响因子：
--
通讯作者：
Nelson WJ
中科院分区：
文献类型：
--
作者：
Spiliotis ET;Hunt SJ;Hu Q;Kinoshita M;Nelson WJ
在上皮细胞中，顶端和基底侧质膜结构域的极化生长和维持依赖于从trans-Golgi网络（TGN）和囊泡递送到质膜的蛋白质分选。Septins是芽殖酵母中极化膜生长所需的丝状GTP酶，但它们是否在上皮极性中起作用尚不清楚。在这里，我们表明，在上皮细胞中，隔蛋白2（SEPT 2）纤维共定位的微管轨道的一个子集组成的聚谷氨酸（polyGlu）微管蛋白，囊泡含有顶端或基底侧蛋白退出TGN沿着这些SEPT 2/polyGlu微管轨道。微管蛋白相关的SEPT 2通过维持polyGlu微管轨道和阻碍微管蛋白结合微管相关蛋白4（MAP 4）来促进囊泡运输。值得注意的是，这一调节步骤是极化的柱状上皮细胞生物发生所必需的;在SEPT 2耗尽后，由于顶端和基底外侧膜蛋白的细胞内积累以及垂直取向的polyGlu微管的丢失，细胞变得短且成纤维细胞形状。我们认为，分隔蛋白耦合的微管细胞骨架后高尔基体囊泡运输所需的极化上皮细胞的形态发生。
In epithelial cells, polarized growth and maintenance of apical and basolateral plasma membrane domains depend on protein sorting from the trans-Golgi network (TGN) and vesicle delivery to the plasma membrane. Septins are filamentous GTPases required for polarized membrane growth in budding yeast, but whether they function in epithelial polarity is unknown. Here, we show that in epithelial cells septin 2 (SEPT2) fibers colocalize with a subset of microtubule tracks composed of polyglutamylated (polyGlu) tubulin, and that vesicles containing apical or basolateral proteins exit the TGN along these SEPT2/polyGlu microtubule tracks. Tubulin-associated SEPT2 facilitates vesicle transport by maintaining polyGlu microtubule tracks and impeding tubulin binding of microtubule-associated protein 4 (MAP4). Significantly, this regulatory step is required for polarized, columnar-shaped epithelia biogenesis; upon SEPT2 depletion, cells become short and fibroblast-shaped due to intracellular accumulation of apical and basolateral membrane proteins, and loss of vertically oriented polyGlu microtubules. We suggest that septin coupling of the microtubule cytoskeleton to post-Golgi vesicle transport is required for the morphogenesis of polarized epithelia.
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影响因子：
16
作者：
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DOI：
10.1083/jcb.200408165
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期刊：
The Journal of cell biology
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