Repression of cell-cell fusion by components of the C. elegans vacuolar ATPase complex.
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.
Kontani
Kenji
K
Department of MCD Biology, Neuroscience Research Institute, University of California, Santa Barbara, 93106, USA.
Moskowitz
Ivan P G
IP
Rothman
Joel H
JH
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002459:Cell Fusion; D017238:Genes, Helminth; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D021122:Protein Subunits; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; D021122:Protein Subunits; C506985:vha-11 protein, C elegans; C506986:vha-2 protein, C elegans; C506987:vha-3 protein, C elegans; D025262:Vacuolar Proton-Translocating ATPases; C506981:unc-32 protein, C elegans