Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN.

Protein complexes containing CYFIP/Sra/PIR121 coordinate Arf1 and Rac1 signalling during clathrin-AP-1-coated carrier biogenesis at the TGN.
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DOI:
10.1038/ncb2034
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发表时间:
2010-04
影响因子:
21.3
通讯作者:
Hoflack, Bernard
Hoflack, Bernard
中科院分区:
生物学1区
文献类型:
--
作者:
Anitei, Mihaela;Stange, Christoph;Parshina, Irina;Baust, Thorsten;Schenck, Annette;Raposo, Graca;Kirchhausen, Tomas;Hoflack, Bernard

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肌动蛋白动力学是一个严格调控的过程,涉及各种细胞事件,包括运输载体生物发生,例如连接跨高尔基体网络 (TGN) 和内吞途径的网格蛋白、AP1 涂层载体。然而,TGN 运输过程中协调外壳组装、膜和肌动蛋白重塑的机制仍然知之甚少。在这里,我们表明 ARF1 GTPase 同步网格蛋白-AP-1 外壳和包含 CYFIP(Sra,PIR121)的蛋白质复合物的 TGN 关联,CYFIP 是一种与智力低下相关的网格蛋白重链结合蛋白。 RAC1 GTPase 及其交换因子 β-PIX 激活这些复合物,允许 N-WASP 和 ARP2/3 依赖性肌动蛋白向膜聚合,从而促进小管形成。这些现象可以使用合成膜来重现。这种基于蛋白质网络的机制促进了通过招募涂层和含有 CYFIP(Sra,PIR121)的复合物的 ARF1 依赖性膜引发与 RAC1 依赖性肌动蛋白聚合之间的顺序协调,并在网格蛋白、AP1 涂层载体生物发生的早期阶段提供互补但独立的调节水平。
Actin dynamics is a tightly regulated process involved in various cellular events including transport carrier biogenesis such as clathrin-, AP1-coated carriers connecting the trans-Golgi network (TGN) and the endocytic pathway. However, the mechanisms coordinating coat assembly, membrane and actin remodeling during post-TGN transport remain poorly understood. Here, we show that the ARF1 GTPase synchronizes the TGN association of clathrin-AP-1 coats and protein complexes comprising CYFIP (Sra, PIR121), a clathrin heavy chain binding protein associated with mental retardation. The RAC1 GTPase and its exchange factor β-PIX activate these complexes allowing N-WASP- and ARP2/3-dependent actin polymerization towards membranes thus promoting tubule formation. These phenomena can be recapitulated using synthetic membranes. This protein-network-based mechanism facilitates the sequential coordination between ARF1-dependent membrane priming via recruitment of coats and CYFIP (Sra, PIR121)-containing complexes, and RAC1-dependent actin polymerization and provides complementary but independent levels of regulation during early stages of clathrin-, AP1-coated carrier biogenesis.
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