Fus-1 Gene May Be Drug Target

Researchers working with the nematode C elegans as a model organism have found that cells in mutants lacking the fus-1 gene fuse incorrectly. These results imply that this gene may be a target for drugs designed to enhance organ regeneration by stem cells, prevent the progression of cancer, or control fertility.

Fus-1 encodes the e subunit of vacuolar ATPase (V-ATPase). It is localized to the apical plasma membrane in all epidermal cells potentiated to undergo fusion, whereas it is virtually undetectable in nonfusing seam cells. Investigators at the University of California, Santa Barbara (USA) reported in the May 2005 issue of Developmental Cell that the fus-1 gene was essential to repress fusion of epidermal cells in C elegans. In mutants lacking fus-1, all epidermal cells, except the lateral seam cells, inappropriately fused into a single large syncytium (a multinucleated mass of cytoplasm not separated into individual cells). This hyperfusion required EFF-1, an integral membrane protein essential for fusion of epidermal cells into discrete syncytia.

Senior author Dr. Joel H. Rothman, professor of molecular, cellular, and developmental biology at the University of California, Santa Barbara, said, "When a cell fuses with others, it loses its individuality, but it can also adopt a new career, either productive, as when stem cells regenerate organs, or sinister, as in cancer metastasis.”

Dr. Rothman and his colleagues concluded that their findings raised the possibility of manipulating cell fusion by altering V-ATPase activity.



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