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Actin-Propelled Invasive Membrane Protrusions Promote Fusogenic Protein Engagement During Cell-Cell Fusion

Science  19 Apr 2013:
Vol. 340, Issue 6130, pp. 359-363
DOI: 10.1126/science.1234781

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To Fuse or Not to Fuse?

Cell-cell fusion is poorly understood, although we know that in the nematode, Caenorhabditis elegans, it involves cell-surface fusogens and in the fly, Drosophila, the actin cytoskeleton plays a role. Shilagardi et al. (p. 359) reconstituted a high-efficiency, inducible cell-fusion culture system, in which they found that the C. elegans fusogen, Eff-1, induced a low level of cell-cell fusion that was enhanced by coexpression with a cell adhesion molecule, Sticks and stones (Sns), required for myoblast fusion in Drosophila. Sns-enhanced cell-cell fusion was mediated by dynamic actin polymerization that generated invasive membrane protrusions at sites of fusion.

Abstract

Cell-cell fusion is critical for the conception, development, and physiology of multicellular organisms. Although cellular fusogenic proteins and the actin cytoskeleton are implicated in cell-cell fusion, it remains unclear whether and how they coordinate to promote plasma membrane fusion. We reconstituted a high-efficiency, inducible cell fusion culture system in the normally nonfusing Drosophila S2R+ cells. Both fusogenic proteins and actin cytoskeletal rearrangements were necessary for cell fusion, and in combination they were sufficient to impart fusion competence. Localized actin polymerization triggered by specific cell-cell or cell-matrix adhesion molecules propelled invasive cell membrane protrusions, which in turn promoted fusogenic protein engagement and plasma membrane fusion. This de novo cell fusion culture system reveals a general role for actin-propelled invasive membrane protrusions in driving fusogenic protein engagement during cell-cell fusion.

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