The retromer component SNX6 interacts with dynactin p150Glued and mediates endosome-to-TGN transport  

作　　者：Zhi Hong Yanrui Yang Cheng Zhang Yang Niu Ke Li Xi Zhao Jia-JiaLiu 

机构地区：[1]Key Laboratory of Molecular and Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China [2]Graduate School, Chinese Academy of Sciences, Beijing 100039, China

出　　处：《Cell Research》2009年第12期1334-1349,共16页细胞研究（英文版）

基　　金：We thank Yingfang Liu （Institute of Biophysics, Chinese Acad- emy of Sciences） for advice on PX domain structure and SNX6 mutations. We are particularly grateful to Yanmin Yang （Stanford University, USA） for insightful discussions and the Flag-MAP1B LC construct. We also thank Juan S Bonifacino （NIH, USA） for the rabbit anti-CI-MPR antibody, Hiroyoshi Ariga （Hokkaido University, Japan） for Flag- and HA-tagged human SNX6 overexpression constructs, and Li Yu （Tsinghua University, China） for the YFP-EEA1 expression construct. We thank Chonglin Yang （Institute of Genetics and Developmental Biology, Chinese Academy of Sciences）, Dahua Chen （Institute of Zoology, Chinese Academy of Sciences） and Li Yu for critical reading of the manuscript. This work was supported by grants from the National Natural Science Foundation of China （30770675） and Chinese Academy of Sciences （KSCX1-YW-R-37）. J-J Liu is supported by the CAS 100-Tal- ents Program.

摘　　要：The retromer is a protein complex that mediates retrograde transport of transmembrane cargoes from endosomes to the trans-Golgi network （TGN）. It is comprised of a cargo-selection subcomplex of Vps26, Vps29 and Vps35 and a membrane-binding coat subcomplex of sorting nexins （SNXs）. Previous studies identified SNX1/2 as one of the components of the SNX subcomplex, and SNX5/6 as candidates for the second SNX. How the retromer-associated cargoes are recognized and transported by molecular motors are largely unknown. In this study, we found that one of SNX1/2＇s dimerization partners, SNX6, interacts with the p150Gued subunit of the dynein/dynactin motor complex. We present evidence that SNX6 is a component of the retromer, and that recruitment of the motor complex to the membrane-associated retromer requires the SNX6-pl50Gued interaction. Disruption of the SNX6-pl50Glued interaction causes failure in formation and detachment of the tubulovesicular sorting structures from endosomes and results in block of CI-MPR retrieval from endosomes to the TGN. These observations indicate that in addition to SNX1/2, SNX6 in association with the dynein/dynactin complex drives the formation and movement of tubular retrograde intermediates.

关 键 词：sorting nexin RETROMER p 150Glued retrograde transport dynein/dynactin CI-MPR 

分 类 号：TP391.9[自动化与计算机技术—计算机应用技术] S511[自动化与计算机技术—计算机科学与技术]