Coronin2A links actin-based endosomal processes to the EHD1 fission machinery.
Coronin2A links actin-based endosomal processes to the EHD1 fission machinery.
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DOI：
10.1091/mbc.e21-12-0624
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发表时间：
2022-10-01
影响因子：
3.3
通讯作者：
Caplan, Steve
中科院分区：
文献类型：
--
作者：
Dhawan, Kanika;Naslavsky, Naava;Caplan, Steve
从内体分裂的运输囊泡是一个关键的步骤，在回收的脂质和受体的质膜，但这一过程仍然知之甚少。虽然裂变机制的关键组成部分，包括肌动蛋白细胞骨架和ATP酶Eps15同源结构域蛋白1（EHD 1），已被牵连在内体裂变，这一过程是如何协调调节是未知的。我们已经确定了肌动蛋白调节蛋白Coronin2A（CORO2A）作为一种新的EHD 1相互作用的合作伙伴。CORO2A定位于应力纤维和肌动蛋白微丝，但也可以观察到在内体结构上与EHD 1部分重叠。siRNA敲除CORO2A导致扩大的片层样肌动蛋白丰富的突起，与其他冠状蛋白家族蛋白在减弱肌动蛋白分支中的作用一致。此外，CORO2A耗竭也导致网格蛋白依赖性货物的内化显著减少，但对网格蛋白非依赖性货物的摄取几乎没有影响，突出了分支肌动蛋白对不同内吞模式的作用的关键差异。然而，需要CORO2A的网格蛋白不依赖货物的再循环，其消耗导致扩大的内体，支持CORO2A的作用，内体囊泡的分裂。我们的数据支持CORO2A在协调EHD1内体分裂和再循环中的新作用。
Fission of transport vesicles from endosomes is a crucial step in the recycling of lipids and receptors to the plasma membrane, but this process remains poorly understood. Although key components of the fission machinery, including the actin cytoskeleton and the ATPase Eps15 homology domain protein 1 (EHD1), have been implicated in endosomal fission, how this process is coordinately regulated is not known. We have identified the actin regulatory protein Coronin2A (CORO2A) as a novel EHD1 interaction partner. CORO2A localizes to stress fibers and actin microfilaments but also can be observed in partial overlap with EHD1 on endosomal structures. siRNA knockdown of CORO2A led to enlarged lamellae-like actin-rich protrusions, consistent with a role of other Coronin family proteins in attenuating actin-branching. Moreover, CORO2A depletion also caused a marked decrease in the internalization of clathrin-dependent cargo but had little impact on the uptake of clathrin-independent cargo, highlighting key differences in the role of branched actin for different modes of endocytosis. However, CORO2A was required for recycling of clathrin-independent cargo, and its depletion led to enlarged endosomes, supporting a role for CORO2A in the fission of endosomal vesicles. Our data support a novel role for CORO2A in coordinating endosomal fission and recycling with EHD1.