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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation
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Mannose receptor polyubiquitination regulates endosomal recruitment of p97 and cytosolic antigen translocation for cross-presentation

机译：甘露糖受体多聚泛素调节内源性p97募集和胞浆抗原易位交叉展示

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摘要

The molecular mechanisms regulating noncanonical protein trans port across cellular membranes are poorly understood. Cross presentation of exogenous antigens on MHC I molecules by dendritic cells (DCs) generally requires antigen translocation from the endosomal compartment into the cytosol for proteasomal degradation. In this study, we demonstrate that such translocation is controlled by the endocytic receptor and regulated by ubiquiti nation. Antigens internalized by the mannose receptor (MR), an endocytic receptor that targets its ligands specifically toward cross-presentation, were translocated into the cytosol only after attachment of a Iysin48-linked polyubiquitin chain to the cytosolic region of the MR. Furthermore, we identify TSG101 as a central regulator of MR ubiquitination and antigen translocation. Impor tantly, we demonstrate that MR polyubiquitination mediates the recruitment of p97, a member of the ER-associated degradation machinery that provides the driving force for antigen transloca tion, toward the endosomal membrane, proving the central role of the endocytic receptor and its ubiquitination in antigen trans location.
机译：调节跨细胞膜非规范蛋白质运输的分子机制了解甚少。树突状细胞（DC）将外源抗原交叉呈递到MHC I分子上，通常需要将抗原从内体区室转移到胞质溶胶中以进行蛋白酶体降解。在这项研究中，我们证明这种易位是由内吞受体控制，并由遍在国家调节。甘露糖受体（MR）（一种将其配体专门针对交叉呈递的内吞性受体）内化的抗原仅在将伊霉素48连接的多聚泛素链连接到MR的胞质区域后才转移到胞质溶胶中。此外，我们确定TSG101为MR泛素化和抗原转运的中央调节器。重要的是，我们证明了MR多聚泛素介导了p97的募集，p97是ER相关降解机制的成员，为抗原向内体膜的转运提供了驱动力，证明了内吞受体及其泛素化在其中的核心作用抗原反式定位。

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    Matthias Zehner; Achmet Imam Chasan; Verena Schuette; Maria Embgenbroich; Thomas Quast; Waldemar Kolanus; Sven Burgdorf;

  • 作者单位

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

    Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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