Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process
Internalization of large double-membrane intercellular vesicles by a clathrin-dependent endocytic process
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DOI：
10.1091/mbc.e06-06-0487
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发表时间：
2007-02-01
影响因子：
3.3
通讯作者：
Falk, Matthias M.
中科院分区：
文献类型：
--
作者：
Piehl, Michelle;Lehmann, Corinna;Falk, Matthias M.
除了在囊泡内吞作用中的作用得到充分证实外，网格蛋白还与病毒、病原菌甚至乳胶珠等大颗粒的内化有关。我们发现了一种额外的网格蛋白依赖性内吞过程，该过程导致细胞侧膜上通过间隙连接（GJ）耦合的大型双膜囊泡的内化。 GJ 通道桥接相对的细胞膜，介导电流和信号分子在细胞之间的直接转移。在这里，我们报告整个 GJ 斑块（GJ 通道簇）可以内化形成大型双膜囊泡，以前称为环形间隙连接（AGJ）。这些内化的 AGJ 囊泡细分为较小的囊泡，并通过内/溶酶体途径降解。机制分析表明，网格蛋白依赖性内吞机制组件，包括网格蛋白本身、替代网格蛋白适配器 Dab2、动力、肌球蛋白-VI 和肌动蛋白，参与这些大的细胞间双膜囊泡的内化、向内运动和降解。这些发现有助于理解网格蛋白的众多新兴功能。
Beyond its well-documented role in vesicle endocytosis, clathrin has also been implicated in the internalization of large particles such as viruses, pathogenic bacteria, and even latex beads. We have discovered an additional clathrin-dependent endocytic process that results in the internalization of large, double-membrane vesicles at lateral membranes of cells that are coupled by gap junctions (GJs). GJ channels bridge apposing cell membranes to mediate the direct transfer of electrical currents and signaling molecules from cell to cell. Here, we report that entire GJ plaques, clusters of GJ channels, can be internalized to form large, double-membrane vesicles previously termed annular gap junctions (AGJs). These internalized AGJ vesicles subdivide into smaller vesicles that are degraded by endo/lysosomal pathways. Mechanistic analyses revealed that clathrin-dependent endocytosis machinery-components, including clathrin itself, the alternative clathrin-adaptor Dab2, dynamin, myosin-VI, and actin are involved in the internalization, inward movement, and degradation of these large, intercellular double-membrane vesicles. These findings contribute to the understanding of clathrin's numerous emerging functions.