Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes
Selective enrichment of tetraspan proteins on the internal vesicles of multivesicular endosomes and on exosomes secreted by human B-lymphocytes
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DOI：
10.1074/jbc.273.32.20121
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发表时间：
1998-08-07
影响因子：
4.8
通讯作者：
Geuze, HJ
中科院分区：
文献类型：
--
作者：
Escola, JM;Kleijmeer, MJ;Geuze, HJ
协会的主要组织相容性复合体（MHC）II类分子与肽发生在一系列的内吞空泡，称为MHC II类富集区室（MIIC）。形态学标准已经定义了几种类型的MIIC，包括多泡MIIC，其由被限制膜包围的50-60-nm囊泡组成。多囊泡MIIC可以与质膜融合，从而将其内部囊泡释放到细胞外空间中。外部化的囊泡，称为外来体，携带MHC II类，可以在体外刺激T细胞。在这项研究中，我们发现外泌体富含共刺激分子CD 86和几种四斯潘蛋白，包括CD 37，CD 53，CD 63，CD 81和CD 82。有趣的是，这些分子的亚细胞定位显示它们集中在多泡MIIC的内膜上。和Lamp-a主要定位于界膜，并且在MIIC的内膜上和外泌体上几乎检测不到。因为多泡MIIC的内囊泡被认为起源于界膜的向内出芽，所以膜蛋白在MIIC的内膜和界膜上的差异分布必须由活性蛋白分选驱动。
Association of major histocompatibility complex (MHC) class II molecules with peptides occurs in a series of endocytic vacuoles, termed MHC class II-enriched compartments (MIICs). Morphological criteria have defined several types of MIICs, including multivesicular MIICs, which are composed of 50-60-nm vesicles surrounded by a limiting membrane. Multivesicular MIICs can fuse with the plasma membrane, thereby releasing their internal vesicles into the extracellular space. The externalized vesicles, termed exosomes, carry MHC class II and can stimulate T-cells in, vitro. In this study, we show that exosomes are enriched in the co-stimulatory molecule CD86 and in several tetraspan proteins, including CD37, CD53, CD63, CD81, and CD82, Interestingly, subcellular localization of these molecules revealed that they were concentrated on the internal membranes of multivesicular MIICs, In contrast to the tetraspans, other membrane proteins of MIICs, such as HLA-DM, Lamp-1, and Lamp-a, were mainly localized to the limiting membrane and mere hardly detectable on the internal membranes of MIICs nor on exosomes, Because internal vesicles of multivesicular MIICs are thought to originate from inward budding of the limiting membrane, the differential distribution of membrane proteins on the internal and limiting membranes of MIICs has to be driven by active protein sorting.