Brief Residence at the Plasma Membrane of the MHC Class I-Related Chain B Is Due to Clathrin-Mediated Cholesterol-Dependent Endocytosis and Shedding
Brief Residence at the Plasma Membrane of the MHC Class I-Related Chain B Is Due to Clathrin-Mediated Cholesterol-Dependent Endocytosis and Shedding
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DOI：
10.4049/jimmunol.0800713
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发表时间：
2009-04-15
影响因子：
4.4
通讯作者：
Vales-Gomez, Mar
中科院分区：
文献类型：
--
作者：
Agueera-Gonzalez, Sonia;Boutet, Philippe;Vales-Gomez, Mar
激活受体NKG 2D识别靶细胞表面的MHC I类相关链（MIC）分子，导致免疫效应细胞溶解它们。NKG 2D配体的上调与应激广泛相关，尽管控制这些分子在质膜上存在的详细分子机制尚不清楚。为了研究控制人NKG 2D配体MICB表面表达的翻译后机制，我们研究了该分子的亚细胞定位和运输。我们发现，在几个细胞系统中，MICB分子在细胞表面上的表达伴随着该分子在trans-Golgi网络和晚期内体相关隔室中的细胞内积累。令人惊讶的是，MICB在质膜上的半衰期比MHC分子短得多，这取决于再循环到内部区室和脱落到细胞外介质。MICB的内化部分依赖于网格蛋白，但重要的是，膜的脂质环境在这一过程中也起着至关重要的作用。我们认为，MICB在质膜的短暂居留调节，至少部分地，这种分子在免疫系统中的功能。免疫学杂志，2009，182：4800-4808.
Recognition of MHC class I-related chain (MIC) molecules on the surface of target cells by the activating receptor NKG2D leads to their lysis by immune effector cells. Up-regulation of NKG2D ligands is broadly related to stress, although the detailed molecular mechanisms that control the presence of these molecules at the plasma membrane are unclear. To investigate the posttranslational mechanisms that control surface expression of the human NKG2D ligand MICB, we studied the subcellular localization and trafficking of this molecule. We found that in several cellular systems, the expression of MICB molecules on the cell surface is accompanied by an intracellular accumulation of the molecule in the trans-Golgi network and late endosome-related compartments. Surprisingly, MICB has a much shorter half-life at the plasma membrane than MHC molecules and this depends on both recycling to internal compartments and shedding to the extracellular medium. Internalization of MICB depends partially on clathrin, but importantly, the lipid environment of the membrane also plays a crucial role in this process. We suggest that the brief residence of MICB at the plasma membrane modulates, at least in part, the function of this molecule in the immune system. The Journal of Immunology, 2009, 182: 4800-4808.