Multiple roles for actin in secretory and endocytic pathways.

Multiple roles for actin in secretory and endocytic pathways.
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DOI:
10.1016/j.cub.2021.03.038
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发表时间:
2021-05-24
期刊:
影响因子:
9.2
通讯作者:
Higgs, Henry N.
Higgs, Henry N.
中科院分区:
生物学1区
文献类型:
--
作者:
Chakrabarti, Rajarshi;Lee, Miriam;Higgs, Henry N.

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肌动蛋白丝在哺乳动物的分泌途径和内体动力学中发挥多种作用,包括维持高尔基体结构、从高尔基体网络(trans-Golgi network,TGN)释放膜货物、内吞作用和内体分选动力学。此外,TGN载体转运和内吞作用在哺乳动物中通过多种机制发生。肌动蛋白可能在至少四种哺乳动物内吞途径(网格蛋白介导的、CLIC/GEEC、FEME和IL 2 R内吞作用)、五种从TGN释放膜的途径(网格蛋白介导的、Rab 6介导的、GOLPH 3介导的、鞘磷脂富集的、Arf 1介导的)和三种内体过程(调节PM再循环、转运至trans-Golgi网络和从早期到晚期内体的过渡)中发挥作用。最后,哺乳动物的高尔基体结构是高度动态的,肌动蛋白可能在这些动态中发挥作用。许多这些过程的一个挑战是需要处理其他膜相关结构,如PM上的皮质肌动蛋白网络或高尔基体周围的基质。Arp 2/3复合物是一个主要的肌动蛋白组装因子在大多数讨论的过程中,但formin和串联WH 2基序的组装因子的作用正在阐明,并预计将扩大与进一步的研究。肌动蛋白的具体作用是没有定义的大多数这些过程中,但很可能是在产生力的膜动力学,无论是通过肌动蛋白聚合本身或肌球蛋白运动活性。从机制上定义这些过程对于理解膜动力学以及利用这些过程的途径(如自噬)是必要的。
Actin filaments play multiple roles in the secretory pathway and endosome dynamics in mammals, including maintenance of Golgi structure, release of membrane cargo from the trans-Golgi network (TGN), endocytosis, and endosomal sorting dynamics. In addition, both TGN carrier transport and endocytosis occur by multiple mechanisms in mammals. Actin likely plays a role in at least four mammalian endocytic pathways (clathrin-mediated, CLIC/GEEC, FEME, and IL2R endocytosis), five pathways for membrane release from the TGN (clathrin-mediated, Rab6-mediated, GOLPH3-mediated, sphingomyelin-enriched, Arf1-mediated), and three processes on endosomes (regulated PM recycling, transport to the trans-Golgi network, and transition from early to late endosomes). Finally, the mammalian Golgi structure is highly dynamic, and actin likely plays roles in these dynamics. One challenge for many of these processes is the need to deal with other membrane-associated structures, such as the cortical actin network on the PM or the matrix that surrounds the Golgi. Arp2/3 complex is a major actin assembly factor in most of the processes discussed, but roles for formins and tandem WH2 motif-containing assembly factors are being elucidated and are anticipated to expand with further study. The specific role for actin is not defined for most of these processes, but is likely to be in generating force for membrane dynamics, either by actin polymerization itself or by myosin motor activity. Defining these processes mechanistically is necessary for understanding membrane dynamics in general, as well as pathways utilizing these processes, such as autophagy.
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