Unveiling the mechanisms of cell-cell fusion

Cell-cell fusion is fundamental to the development and physiology of multicellular organisms, but little is known of its mechanistic underpinnings. Recent studies have revealed that many proteins involved in cell-cell fusion are also required for seemingly unrelated cellular processes such as phagocytosis, cell migration, axon growth, and synaptogenesis. We review advances in understanding cell-cell fusion by contrasting it with virus-cell and intracellular vesicle fusion. We also consider how proteins involved in general aspects of membrane dynamics have been co-opted to control fusion of diverse cell types by coupling with specialized proteins involved in cell-cell recognition, adhesion, and signaling. T he advent of membranes during evolu-tion heralded the appearance of life itself by providing the basic unit of cellular structure and allowing the compartmentaliza-tion of metabolites, ions, organelles, and genetic material. Inherent in the organization of phos