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在体内，多价连接蛋白将WASP和WIP募集到明显的阈值水平后，Arp2/3呈现开关式激活。

Switch-like Arp2/3 activation upon WASP and WIP recruitment to an apparent threshold level by multivalent linker proteins in vivo.

作者信息

Sun Yidi, Leong Nicole T, Jiang Tommy, Tangara Astou, Darzacq Xavier, Drubin David G

机构信息

Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States.

出版信息

Elife. 2017 Aug 16;6:e29140. doi: 10.7554/eLife.29140.

DOI:10.7554/eLife.29140
PMID:28813247
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5559269/
Abstract

Actin-related protein 2/3 (Arp2/3) complex activation by nucleation promoting factors (NPFs) such as WASP, plays an important role in many actin-mediated cellular processes. In yeast, Arp2/3-mediated actin filament assembly drives endocytic membrane invagination and vesicle scission. Here we used genetics and quantitative live-cell imaging to probe the mechanisms that concentrate NPFs at endocytic sites, and to investigate how NPFs regulate actin assembly onset. Our results demonstrate that SH3 (Src homology 3) domain-PRM (proline-rich motif) interactions involving multivalent linker proteins play central roles in concentrating NPFs at endocytic sites. Quantitative imaging suggested that productive actin assembly initiation is tightly coupled to accumulation of threshold levels of WASP and WIP, but not to recruitment kinetics or release of autoinhibition. These studies provide evidence that WASP and WIP play central roles in establishment of a robust multivalent SH3 domain-PRM network in vivo, giving actin assembly onset at endocytic sites a switch-like behavior.

摘要

由诸如WASP等成核促进因子（NPF）激活的肌动蛋白相关蛋白2/3（Arp2/3）复合物，在许多肌动蛋白介导的细胞过程中发挥重要作用。在酵母中，Arp2/3介导的肌动蛋白丝组装驱动内吞膜内陷和囊泡分裂。在这里，我们使用遗传学和定量活细胞成像技术来探究将NPF集中在内吞位点的机制，并研究NPF如何调节肌动蛋白组装的起始。我们的结果表明，涉及多价连接蛋白的SH3（Src同源结构域3）结构域与富含脯氨酸基序（PRM）的相互作用，在将NPF集中在内吞位点方面起着核心作用。定量成像表明，有效的肌动蛋白组装起始与WASP和WIP阈值水平的积累紧密相关，而与募集动力学或自抑制的释放无关。这些研究提供了证据，表明WASP和WIP在体内建立强大的多价SH3结构域-PRM网络中起核心作用，使内吞位点的肌动蛋白组装起始具有类似开关的行为。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/f995c987be45/elife-29140-fig5-figsupp3.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/3a7408f0c6a6/elife-29140-fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/d078d0bd0b53/elife-29140-fig1-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/4c8e7449cf98/elife-29140-fig1-figsupp2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/eed2f9112baf/elife-29140-fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/a19f6753cd91/elife-29140-fig2-figsupp1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/a1dbc8581ee5/elife-29140-fig4-figsupp1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8aea/5559269/168dd2a171f7/elife-29140-fig5.jpg
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