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FIP1/RCP 与 Golgin-97 的结合调节了从回收内体到反式高尔基体网络的逆行运输。

FIP1/RCP binding to Golgin-97 regulates retrograde transport from recycling endosomes to the trans-Golgi network.

机构信息

Department of Cell and Developmental Biology, School of Medicine, University of Colorado Denver, Aurora, CO 80045, USA.

出版信息

Mol Biol Cell. 2010 Sep 1;21(17):3041-53. doi: 10.1091/mbc.E10-04-0313. Epub 2010 Jul 7.

DOI:10.1091/mbc.E10-04-0313
PMID:20610657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2929997/
Abstract

Many proteins are retrieved to the trans-Golgi Network (TGN) from the endosomal system through several retrograde transport pathways to maintain the composition and function of the TGN. However, the molecular mechanisms involved in these distinct retrograde pathways remain to be fully understood. Here we have used fluorescence and electron microscopy as well as various functional transport assays to show that Rab11a/b and its binding protein FIP1/RCP are both required for the retrograde delivery of TGN38 and Shiga toxin from early/recycling endosomes to the TGN, but not for the retrieval of mannose-6-phosphate receptor from late endosomes. Furthermore, by proteomic analysis we identified Golgin-97 as a FIP1/RCP-binding protein. The FIP1/RCP-binding domain maps to the C-terminus of Golgin-97, adjacent to its GRIP domain. Binding of FIP1/RCP to Golgin-97 does not affect Golgin-97 recruitment to the TGN, but appears to regulate the targeting of retrograde transport vesicles to the TGN. Thus, we propose that FIP1/RCP binding to Golgin-97 is required for tethering and fusion of recycling endosome-derived retrograde transport vesicles to the TGN.

摘要

许多蛋白质通过几种逆行运输途径从内体系统中回收至反式高尔基体网络（TGN），以维持 TGN 的组成和功能。然而，这些不同逆行途径中涉及的分子机制仍有待充分理解。在这里，我们使用荧光和电子显微镜以及各种功能运输测定法表明，Rab11a/b 及其结合蛋白 FIP1/RCP 均是 TGN38 和志贺毒素从早期/再循环内体逆行递送至 TGN 所必需的，但对于从晚期内体回收甘露糖-6-磷酸受体则不是必需的。此外，通过蛋白质组学分析，我们鉴定出 Golgin-97 是 FIP1/RCP 的结合蛋白。FIP1/RCP 的结合域位于 Golgin-97 的 C 末端，紧邻其 GRIP 结构域。FIP1/RCP 与 Golgin-97 的结合并不影响 Golgin-97 向 TGN 的募集，但似乎调节逆行运输囊泡向 TGN 的靶向。因此，我们提出 FIP1/RCP 与 Golgin-97 的结合对于将再循环内体衍生的逆行运输囊泡锚定和融合至 TGN 是必需的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/d4918b6b85c0/zmk0171095580010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/d4918b6b85c0/zmk0171095580010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/abadc00d8364/zmk0171095580002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/8de5c2c13802/zmk0171095580004.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/8dbf6b339bcc/zmk0171095580006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7742/2929997/d4918b6b85c0/zmk0171095580010.jpg

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