Cell–cell fusogens are glycoproteins that facilitate the fusion of cell to cell membranes. Cell-cell fusion is critical for the merging of gamete genomes and development of organs in multicelluar organisms. It drives cell membrane protrustions and fusogenic protein engagement.
EFF-AFF are the identifiers of type 1 glycoproteins that make up cell-cell fusogens. They were first identified when EFF1 mutants were found to block cell fusion in all epidermal and vulval epithelia in the roundworm, Caenorhabditis elegans. EFF-AFF is a family of type I membrane glycoproteins that act as cell–cell fusogens, named from 'Anchor cell fusion failure'. However, fusion between the anchor-cell and the (uterine seam) utse syncytium that establishes a continuous uterine-vulval tube proceeds normally in eff-1 mutants and thus Aff1 was established as necessary for this and the fusion of heterologous cells inC. elegans. The transmembrane forms of these proteins, like most viral fusogens, possess an N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. A striking conservation in the position and number of all 16 cysteines in the extracellular portion of EFF-AFF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity. C. elegans AFF-1 and EFF-1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle.