TBC1D24 regulates recycling of clathrin-independent cargo proteins mediated by tubular recycling endosomes

TBC1D24 regulates recycling of clathrin-independent cargo proteins mediated by tubular recycling endosomes
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TBC1D24 调节由管状回收内体介导的网格蛋白独立货物蛋白的回收

DOI:
10.1016/j.bbrc.2020.05.007
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发表时间:
2020
期刊:
Biochem Biophys Res Commun
影响因子:
--
通讯作者:
Funakoshi Y.
Funakoshi Y.
中科院分区:
--
文献类型:
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作者:
Kim Nguyen NT;Ohbayashi N;Kanaho Y;Funakoshi Y.

文献摘要

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许多质膜蛋白通过网状蛋白非依赖性内吞作用进入细胞。RAB家族的小分子GTP酶在CIE和随后的货物蛋白的细胞内转运中起着关键作用。在这里,我们提供的证据表明,包含一个非典型的Rab间隙结构域的TBC1D24有助于形成管状循环内小体(Tres),这是CIE在HeLa细胞中货物运输途径的一个标志。在HeLa细胞中过表达TBC1D24显著增加了携带CIE货运蛋白的TrE,而缺失TBC1D24则抑制了TrE的形成,并延缓了CIE货运蛋白回到质膜的循环。我们还发现,TBC1D24与Rab22A结合,通过Rab22A调控TrE介导的CIE货物回收。这些发现为CIE货物贩运的监管机制提供了洞察力。
Many plasma membrane proteins enter cells by clathrin-independent endocytosis (CIE). Rab family small GTPases play pivotal roles in CIE and following intracellular trafficking of cargo proteins. Here, we provide evidence that TBC1D24, which contains an atypical Rab GAP domain, facilitates formation of tubular recycling endosomes (TREs) that are a hallmark of the CIE cargo trafficking pathway in HeLa cells. Overexpression of TBC1D24 in HeLa cells dramatically increased TREs loaded with CIE cargo proteins, while deletion ofTBC1D24impaired TRE formation and delayed the recycling of CIE cargo proteins back to the plasma membrane. We also found that TBC1D24 binds to Rab22A, through which TBC1D24 regulates TRE-mediated CIE cargo recycling. These findings provide insight into regulatory mechanisms for CIE cargo trafficking.