Cooperative recruitment of dynamin and BIN/amphiphysin/Rvs (BAR) domain-containing proteins leads to GTP-dependent membrane scission.
Cooperative recruitment of dynamin and BIN/amphiphysin/Rvs (BAR) domain-containing proteins leads to GTP-dependent membrane scission.
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DOI：
10.1074/jbc.m112.444869
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发表时间：
2013-03-01
期刊：
影响因子：
--
通讯作者：
McMahon HT
中科院分区：
文献类型：
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作者：
Meinecke M;Boucrot E;Camdere G;Hon WC;Mittal R;McMahon HT
背景：动力蛋白和BAR结构域蛋白是网状蛋白介导的内吞作用和其他膜转运活动的主要成分。结果：Dynamin通过BAR结构域蛋白被募集到膜上，而后者又依赖于与Dynamin的相互作用而与膜结合。结论：Dynamin和bar结构域蛋白与膜结合是协同作用的，可刺激Dynamin和GTP依赖的膜断裂。意义：我们的结果暗示了动力素和BAR结构域蛋白的协同作用，以促进GTP依赖的囊泡释放。Dynamin介导各种膜分裂事件，包括网状蛋白包裹的小泡的断裂。在这里，我们提供了动力蛋白与BIN/两体蛋白/RVS(BAR)蛋白、内亲素和两体蛋白合作膜募集的直接证据。令人惊讶的是，由于杆-膜相互作用的自动抑制，亲内素和两栖类药物在膜上的募集也依赖于与动力蛋白的结合。与体外相互募集一致，内亲素和两栖类蛋白的耗尽使细胞质膜上的动力素募集显著减少，反之，动力素的耗竭显著减少了内亲蛋白的募集。此外，观察到两栖类药物的耗竭严重抑制了笼状蛋白介导的内吞作用。此外，Bar结构域蛋白显著增加了Dynamin对GTP依赖的膜断裂。因此，BAR结构域蛋白和动力蛋白在膜募集和依赖GTP的囊泡破裂中发挥协同作用。
Background: Dynamin and BAR domain proteins are major components of clathrin-mediated endocytosis and other membrane-trafficking events. Results: Dynamin is recruited to membranes by BAR domain proteins, which in turn rely on interaction with dynamin to bind membranes. Conclusion: Membrane binding by dynamin and BAR domain proteins is cooperative and stimulates dynamin and GTP-dependent membrane scission. Significance: Our results imply synergy of dynamin and BAR domain proteins to promote GTP-dependent vesicle release. Dynamin mediates various membrane fission events, including the scission of clathrin-coated vesicles. Here, we provide direct evidence for cooperative membrane recruitment of dynamin with the BIN/amphiphysin/Rvs (BAR) proteins, endophilin and amphiphysin. Surprisingly, endophilin and amphiphysin recruitment to membranes was also dependent on binding to dynamin due to auto-inhibition of BAR-membrane interactions. Consistent with reciprocal recruitment in vitro, dynamin recruitment to the plasma membrane in cells was strongly reduced by concomitant depletion of endophilin and amphiphysin, and conversely, depletion of dynamin dramatically reduced the recruitment of endophilin. In addition, amphiphysin depletion was observed to severely inhibit clathrin-mediated endocytosis. Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. Thus, BAR domain proteins and dynamin act in synergy in membrane recruitment and GTP-dependent vesicle scission.