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首页> 外文期刊>Nature cell biology >Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network
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Phosphoinositide-mediated clathrin adaptor progression at the trans-Golgi network

机译:反高尔基体网络中磷脂酰肌醇介导的网格蛋白衔接子进程

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摘要

Clathrin-coated vesicles mediate endocytosis and transport between the trans-Golgi network (TGN) and endosomes in eukaryotic cells. Clathrin adaptors play central roles in coat assembly, interacting with clathrin, cargo and membranes. Two main types of clathrin adaptor act in TGN-endosome traffic: GGA proteins and the AP-1 complex. Here we characterize the relationship between GGA proteins, AP-1 and other TGN clathrin adaptors using live-cell and super-resolution microscopy in yeast. We present evidence that GGA proteins and AP-1 are recruited sequentially in two waves of coat assembly at the TGN. Mutations that decrease phosphatidylinositol 4-phosphate (PtdIns(4)P) levels at the TGN slow or uncouple AP-1 coat assembly from GGA coat assembly. Conversely, enhanced PtdIns(4)P synthesis shortens the time between adaptor waves. Gga2p binds directly to the TGN PtdIns(4)-kinase Pik1p and contributes to Pik1p recruitment. These results identify a PtdIns(4)P-based mechanism for regulating progressive assembly of adaptor-specific clathrin coats at the TGN.
机译:包被网格蛋白的囊泡介导真核细胞中反式高尔基体网络(TGN)和内体之间的内吞和运输。网格蛋白适配器在外套组装中起着核心作用,与网格蛋白,货物和膜相互作用。网格蛋白衔接子的两种主要类型在TGN-内体运输中起作用:GGA蛋白和AP-1复合物。在这里,我们使用酵母中的活细胞和超分辨率显微镜表征了GGA蛋白,AP-1和其他TGN网格蛋白衔接子之间的关系。我们提供的证据表明,在TGN的两次外套组装波中,GGA蛋白和AP-1被顺序招募。突变会降低TGN上的磷脂酰肌醇4-磷酸(PtdIns(4)P)水平,从而使AP-1涂层组件从GGA涂层组件中减慢或脱离。相反,增强的PtdIns(4)P合成缩短了适配器波之间的时间。 Gga2p直接绑定到TGN PtdIns(4)激酶Pik1p,并有助于Pik1p募集。这些结果确定了一种基于PtdIns(4)P的机制,用于调节TGN上的衔接子特异性网格蛋白涂层的逐步组装。

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