Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway
Internalization of MUC1 by anti-MUC1 antibody from cell membrane through the macropinocytotic pathway
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DOI：
10.1016/j.bbrc.2009.08.059
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发表时间：
2009-10-30
影响因子：
3.1
通讯作者：
Kim, Kwang Chul
中科院分区：
文献类型：
--
作者：
Hisatsune, Akinori;Kawasaki, Mitsuru;Kim, Kwang Chul
MUC 1是一种I型跨膜糖蛋白，在多种癌细胞中异常过表达。它被认为是细胞外环境的物理屏障，也是各种细胞外分子的受体。然而，关于MUC 1在与这些分子相互作用期间和之后的命运知之甚少。在本研究中，我们使用抗MUC 1抗体作为相互作用分子，并研究了MUC 1的细胞运输。我们的研究结果表明：（1）抗MUC 1抗体仅在表达MUC 1的细胞中内化，并触发MUC 1的内化和下调;（2）抗MUC 1抗体对MUC 1的内化需要MUC 1的胞质尾区，并被Na+/H+交换抑制剂和Caveola/raft依赖性内化抑制剂抑制，但不被网格蛋白依赖性内化抑制剂抑制。我们的结论是抗体诱导的MUC 1的内化涉及巨胞饮途径。(C)2009爱思唯尔公司All rights reserved.
MUC1 is a type I transmembrane glycoprotein aberrantly overexpressed in various cancer cells. It is thought to serve as a physical barrier from the extracellular environment and also as a receptor for various extracellular molecules. However, little is known about the fate of MUC1 during and after the interaction with these molecules. In the present study, we used anti-MUC1 antibody as an interacting molecule and investigated the cellular trafficking of MUC1. Our results showed that: (1) anti-MUC1 antibody was internalized only in MUC1 expressing cells and triggered internalization and down-regulation of MUC1; (2) the internalization of MUC1 by anti-MUC1 antibody required the cytoplasmic tail of MUC1 and was suppressed by inhibitors of Na+/H+ exchanger, and caveola/raft-dependent internalization, but not by an inhibitor of clathrin-dependent internalization. We conclude that antibody-induced internalization of MUC1 involves the macropinocytotic pathway. (C) 2009 Elsevier Inc. All rights reserved.