Repression of cell-cell fusion by components of the C. elegans vacuolar ATPase complex.

TitleRepression of cell-cell fusion by components of the C. elegans vacuolar ATPase complex.
Publication TypeJournal Article
Year of Publication2005
AuthorsKontani K, Moskowitz IPG, Rothman JH
JournalDev Cell
Date Published2005 May
KeywordsAnimals, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Cell Fusion, Genes, Helminth, Membrane Glycoproteins, Mutation, Protein Subunits, Vacuolar Proton-Translocating ATPases

Cell-cell fusion initiates fertilization, sculpts tissues during animal development, reprograms stem cells to new differentiated states, and may be a key step in cancer progression. While cell fusion is tightly regulated, the mechanisms that limit fusion to appropriate partners are unknown. Here, we report that the fus-1 gene is essential to repress fusion of epidermal cells in C. elegans: in severe fus-1 mutants, all epidermal cells, except the lateral seam cells, inappropriately fuse into a single large syncytium. This hyperfusion requires EFF-1, an integral membrane protein essential for fusion of epidermal cells into discrete syncytia. FUS-1 is localized to the apical plasma membrane in all epidermal cells potentiated to undergo fusion, whereas it is virtually undetectable in nonfusing seam cells. fus-1 encodes the e subunit of the vacuolar H(+)-ATPase (V-ATPase), and loss of other V-ATPase subunits also causes widespread hyperfusion. These findings raise the possibility of manipulating cell fusion by altering V-ATPase activity.

Alternate JournalDev. Cell
PubMed ID15866168
Grant ListCA95943 / CA / NCI NIH HHS / United States
HD37487 / HD / NICHD NIH HHS / United States