Römer Winfried, Berland Ludwig, Chambon Valérie, Gaus Katharina, Windschiegl Barbara, Tenza Danièle, Aly Mohamed R E, Fraisier Vincent, Florent Jean-Claude, Perrais David, Lamaze Christophe, Raposo Graça, Steinem Claudia, Sens Pierre, Bassereau Patricia, Johannes Ludger
Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires, Paris Cedex 05, France.
Nature. 2007 Nov 29;450(7170):670-5. doi: 10.1038/nature05996.
Clathrin seems to be dispensable for some endocytic processes and, in several instances, no cytosolic coat protein complexes could be detected at sites of membrane invagination. Hence, new principles must in these cases be invoked to account for the mechanical force driving membrane shape changes. Here we show that the Gb3 (glycolipid)-binding B-subunit of bacterial Shiga toxin induces narrow tubular membrane invaginations in human and mouse cells and model membranes. In cells, tubule occurrence increases on energy depletion and inhibition of dynamin or actin functions. Our data thus demonstrate that active cellular processes are needed for tubule scission rather than tubule formation. We conclude that the B-subunit induces lipid reorganization that favours negative membrane curvature, which drives the formation of inward membrane tubules. Our findings support a model in which the lateral growth of B-subunit-Gb3 microdomains is limited by the invagination process, which itself is regulated by membrane tension. The physical principles underlying this basic cargo-induced membrane uptake may also be relevant to other internalization processes, creating a rationale for conceptualizing the perplexing diversity of endocytic routes.
网格蛋白对于某些内吞过程似乎并非必不可少，而且在一些情况下，在膜内陷部位未检测到胞质包被蛋白复合物。因此，在这些情况下必须引入新的原理来解释驱动膜形状变化的机械力。在此我们表明，细菌志贺毒素的Gb3（糖脂）结合B亚基在人和小鼠细胞以及模型膜中诱导狭窄的管状膜内陷。在细胞中，能量耗竭以及抑制发动蛋白或肌动蛋白功能时，小管的出现会增加。因此，我们的数据表明，小管切断需要活跃的细胞过程，而不是小管形成。我们得出结论，B亚基诱导脂质重排，有利于负膜曲率，从而驱动向内的膜小管形成。我们的发现支持一种模型，其中B亚基-Gb3微结构域的横向生长受到内陷过程的限制，而内陷过程本身受膜张力调节。这种基本的货物诱导膜摄取背后的物理原理可能也与其他内化过程相关，为理解内吞途径令人困惑的多样性提供了理论依据。
