对细菌毒素吸收进细胞中的一个早期阶段（膜内折的形成）所进行的一项成像研究，显示了一个由货物诱导的机制，该机制也许还适用于其他病原体，如病毒等，并且更普遍地适用于其他细胞内吞事件。研究人员观测到，志贺氏毒素（由痢疾志贺氏菌产生）的B-亚单元通过狭窄的管状膜内折进入细胞。该毒素在管状内折形成之前诱导膜重组。在细胞上，内折独立于被认为与膜变形能力有关的蛋白复合物（如clathrin  和caveolin）而形成，并且还是在细胞能量耗尽时形成的。所以，膜内折依赖于物理原理，能够自然地出现，而不需要复杂的细胞机器，但随后的分离需要细胞因素的参与。

　　原始出处:

　　Nature450, 670-675 (29 November 2007) | doi:10.1038/nature05996; Received 15 August 2007; Accepted 5 October 2007

　　Shiga toxin induces tubular membrane invaginations for its uptake into cells

Winfried Römer1,5, Ludwig Berland2,6, Valérie Chambon1,5, Katharina Gaus8,9, Barbara Windschiegl10, Danièle Tenza3,5, Mohamed R. E. Aly4,7, Vincent Fraisier5, Jean-Claude Florent4,7, David Perrais11, Christophe Lamaze1,5, Graça Raposo3,5, Claudia Steinem10, Pierre Sens12, Patricia Bassereau2,6 & Ludger Johannes1,5

1.                      Institut Curie, Centre de Recherche, Laboratoire Trafic, Signalisation et Ciblage Intracellulaires,

2.                      Laboratoire Physico-Chimie,

3.                      Laboratoire Structure et Compartiments Membranaires,

4.                      Laboratoire Chimie Organique (Vectorisation), 26 rue d'Ulm, 75248 Paris Cedex 05, France

5.                      CNRS UMR144,

6.                      Université P. et M. Curie/CNRS UMR168,

7.                      CNRS UMR176,

8.                      Centre for Vascular Research, University of New South Wales, 2052 Sydney, Australia

9.                      Department of Haematology, Prince of Wales Hospital, 2031 Sydney, Australia

10.                   Institut für Organische und Biomolekulare Chemie, Georg-August Universität, Tammannstr. 2, 37077 Göttingen, Germany

11.                   Laboratoire de Physiologie Cellulaire de la Synapse, CNRS UMR 5091 et Université Bordeaux 2, Institut François Magendie, 33077 Bordeaux, France

12.                   UMR Gulliver CNRS-ESPCI 7083, 10 rue Vauquelin, 75231 Paris Cedex 05, France

Correspondence to: Ludger Johannes1,5 Correspondence and requests for materials should be addressed to L.J. (Email: johannes@curie.fr).

Abstract

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.

                                                      摘自《生物谷》