A role for the Golgi matrix protein giantin in ciliogenesis through control of the localization of dynein-2
A role for the Golgi matrix protein giantin in ciliogenesis through control of the localization of dynein-2
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DOI：
10.1242/jcs.131664
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发表时间：
2013-11-15
影响因子：
4
通讯作者：
Stephens, David J.
中科院分区：
文献类型：
--
作者：
Asante, David;MacCarthy-Morrogh, Lucy;Stephens, David J.
初级纤毛的正确形成对几乎所有细胞和组织的发育和功能都至关重要。纤毛从中心粒母体通过微管核心（轴丝）的延伸而生长，然后轴丝被与质膜连续的特化纤毛膜包围。鞭毛内运输使颗粒沿着轴丝的长度移动以指导纤毛的组装，并且也是适当的纤毛功能所需的。微管马达，细胞质动力蛋白2介导逆行运输沿着轴丝从顶端到基部;动力蛋白2也需要纤毛形成的某些方面。在大多数细胞中，高尔基体位于中心粒附近，纤毛机械的关键成分定位于该细胞器。高尔基体定位的蛋白质也被牵连在纤毛发生和鞭毛内运输。在这里，我们表明，跨膜高尔基体基质蛋白giantin（GOLGB 1）所需的纤毛。我们发现，Giantin是不需要的Rab 11-Rabin 8-Rab 8通路，已牵连在睫状膜形成的早期阶段。相反，我们发现抑制巨蛋白导致动力蛋白-2的中间链WDR 34的错误定位。Giantin或WDR 34的高效消耗导致细胞不能形成初级纤毛。Giantin或WDR 34的部分消耗导致纤毛长度增加，这与Giantin通过动力蛋白-2起作用的概念一致。我们的数据暗示Giantin通过控制动力蛋白-2定位在纤毛发生中。
The correct formation of primary cilia is central to the development and function of nearly all cells and tissues. Cilia grow from the mother centriole by extension of a microtubule core, the axoneme, which is then surrounded with a specialized ciliary membrane that is continuous with the plasma membrane. Intraflagellar transport moves particles along the length of the axoneme to direct assembly of the cilium and is also required for proper cilia function. The microtubule motor, cytoplasmic dynein-2 mediates retrograde transport along the axoneme from the tip to the base; dynein-2 is also required for some aspects of cilia formation. In most cells, the Golgi lies adjacent to the centrioles and key components of the cilia machinery localize to this organelle. Golgi-localized proteins have also been implicated in ciliogenesis and in intraflagellar transport. Here, we show that the transmembrane Golgi matrix protein giantin (GOLGB1) is required for ciliogenesis. We show that giantin is not required for the Rab11-Rabin8-Rab8 pathway that has been implicated in the early stages of ciliary membrane formation. Instead we find that suppression of giantin results in mis-localization of WDR34, the intermediate chain of dynein-2. Highly effective depletion of giantin or WDR34 leads to an inability of cells to form primary cilia. Partial depletion of giantin or of WDR34 leads to an increase in cilia length consistent with the concept that giantin acts through dynein-2. Our data implicate giantin in ciliogenesis through control of dynein-2 localization.