Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway.
Rab34 GTPase mediates ciliary membrane formation in the intracellular ciliogenesis pathway.
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DOI：
10.1016/j.cub.2021.04.075
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发表时间：
2021-07-12
期刊：
影响因子：
--
通讯作者：
Breslow DK
中科院分区：
文献类型：
--
作者：
Ganga AK;Kennedy MC;Oguchi ME;Gray S;Oliver KE;Knight TA;De La Cruz EM;Homma Y;Fukuda M;Breslow DK
初级纤毛是信号传导的重要组织中心，纤毛缺陷导致先天性疾病，统称为纤毛病。初级纤毛通过以细胞类型和组织特异性方式采用的两种途径形成：纤毛从细胞表面生长出来的细胞外途径和新生纤毛首先在细胞内形成的细胞内途径。在暴露于外部环境后，通过细胞内途径形成的纤毛可能具有不同的功能特性，因为它们通常保持凹陷在纤毛袋内。然而，细胞内纤毛发生的确切机制及其与细胞外纤毛发生的相关性仍然知之甚少。在这里，我们表明，Rab34，最近连接到纤毛的一个不好的特点GTdR，是细胞内纤毛发生的选择性介质。我们发现，Rab34是所需的纤毛囊泡在母亲中心粒的形成和Rab34标志着睫状鞘，一个独特的子结构域组装细胞内纤毛。Rab34的活性受其GTP酶域内不同残基的调节，纤毛发生需要Rab34的GTP结合和周转。由于Rab34是在细胞内纤毛发生所特有的组装中间体上发现的，因此我们测试了其在极化MDCK细胞所使用的细胞外途径中的作用。与Rab34特异性作用于细胞内途径一致，MDCK细胞纤毛独立于Rab34及其Parab36。总之，这些发现确立了不同的纤毛发生模式具有不同的分子要求，并揭示Rab34作为睫状膜生物发生的新GTdR介体。不同类型的细胞通过不同的组装途径形成初级纤毛。Ganga等人表明，GTdR ab 34是细胞内纤毛发生途径中而不是细胞外途径中的纤毛膜形成所需的。在细胞内纤毛发生过程中，Rab34被募集到新生纤毛并定位于睫状体鞘。
The primary cilium is an essential organizing center for signal transduction, and ciliary defects cause congenital disorders known collectively as ciliopathies. Primary cilia form by two pathways that are employed in a cell type- and tissue-specific manner: an extracellular pathway in which the cilium grows out from the cell surface and an intracellular pathway in which the nascent cilium first forms inside the cell. After exposure to the external environment, cilia formed via the intracellular pathway may have distinct functional properties, as they often remain recessed within a ciliary pocket., However, the precise mechanism of intracellular ciliogenesis and its relatedness to extracellular ciliogenesis remain poorly understood. Here we show that Rab34, a poorly characterized GTPase recently linked to cilia, is a selective mediator of intracellular ciliogenesis. We find that Rab34 is required for formation of the ciliary vesicle at the mother centriole and that Rab34 marks the ciliary sheath, a unique sub-domain of assembling intracellular cilia. Rab34 activity is modulated by divergent residues within its GTPase domain, and ciliogenesis requires GTP binding and turnover by Rab34. Because Rab34 is found on assembly intermediates that are unique to intracellular ciliogenesis, we tested its role in the extracellular pathway used by polarized MDCK cells. Consistent with Rab34 acting specifically in the intracellular pathway, MDCK cells ciliate independently of Rab34 and its paralog Rab36. Together, these findings establish that different modes of ciliogenesis have distinct molecular requirements and reveal Rab34 as a new GTPase mediator of ciliary membrane biogenesis. Different cell types form primary cilia through different assembly pathways. Ganga et al. show that the GTPase Rab34 is needed for ciliary membrane formation in the intracellular ciliogenesis pathway but not the extracellular pathway. During intracellular ciliogenesis, Rab34 is recruited to nascent cilia and localizes to the ciliary sheath.
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影响因子：
7.2
作者：
Braun DA;Hildebrandt F
通讯作者：
Hildebrandt F
DOI：
10.1073/pnas.1004602107
发表时间：
2010-05-25
影响因子：
11.1
作者：
Lee, Eunice Y.;Ji, Hongkai;Scott, Matthew P.
通讯作者：
Scott, Matthew P.
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
21.3
作者：
通讯作者：
--
影响因子：
30.8
作者：
Breslow DK;Hoogendoorn S;Kopp AR;Morgens DW;Vu BK;Kennedy MC;Han K;Li A;Hess GT;Bassik MC;Chen JK;Nachury MV
通讯作者：
Nachury MV