Kjeken Rune, Egeberg Morten, Habermann Anja, Kuehnel Mark, Peyron Pascale, Floetenmeyer Matthias, Walther Paul, Jahraus Andrea, Defacque Hélène, Kuznetsov Sergei A, Griffiths Gareth
European Molecular Biology Laboratory, D-69117 Heidelberg, Germany.
Mol Biol Cell. 2004 Jan;15(1):345-58. doi: 10.1091/mbc.e03-05-0334. Epub 2003 Nov 14.
Actin is implicated in membrane fusion, but the precise mechanisms remain unclear. We showed earlier that membrane organelles catalyze the de novo assembly of F-actin that then facilitates the fusion between latex bead phagosomes and a mixture of early and late endocytic organelles. Here, we correlated the polymerization and organization of F-actin with phagosome and endocytic organelle fusion processes in vitro by using biochemistry and light and electron microscopy. When membrane organelles and cytosol were incubated at 37 degrees C with ATP, cytosolic actin polymerized rapidly and became organized into bundles and networks adjacent to membrane organelles. By 30-min incubation, a gel-like state was formed with little further polymerization of actin thereafter. Also during this time, the bulk of in vitro fusion events occurred between phagosomes/endocytic organelles. The fusion between latex bead phagosomes and late endocytic organelles, or between late endocytic organelles themselves was facilitated by actin, but we failed to detect any effect of perturbing F-actin polymerization on early endosome fusion. Consistent with this, late endosomes, like phagosomes, could nucleate F-actin, whereas early endosomes could not. We propose that actin assembled by phagosomes or late endocytic organelles can provide tracks for fusion-partner organelles to move vectorially toward them, via membrane-bound myosins, to facilitate fusion.
肌动蛋白与膜融合有关,但其确切机制仍不清楚。我们之前表明,膜细胞器催化F-肌动蛋白的从头组装,然后促进乳胶珠吞噬体与早期和晚期内吞细胞器混合物之间的融合。在这里,我们通过生物化学、光学显微镜和电子显微镜,在体外将F-肌动蛋白的聚合和组织与吞噬体和内吞细胞器融合过程相关联。当膜细胞器和细胞质在37℃下与ATP一起孵育时,细胞质肌动蛋白迅速聚合,并在膜细胞器附近组织成束和网络。孵育30分钟后,形成了一种凝胶状状态,此后肌动蛋白几乎没有进一步聚合。同样在此期间,大部分体外融合事件发生在吞噬体/内吞细胞器之间。肌动蛋白促进了乳胶珠吞噬体与晚期内吞细胞器之间,或晚期内吞细胞器自身之间的融合,但我们未能检测到干扰F-肌动蛋白聚合对早期内体融合的任何影响。与此一致的是,晚期内体与吞噬体一样,可以使F-肌动蛋白成核,而早期内体则不能。我们提出,由吞噬体或晚期内吞细胞器组装的肌动蛋白可以为融合伙伴细胞器提供轨道,使其通过膜结合的肌球蛋白向它们定向移动,以促进融合。