title: RAB-5- and DYNAMIN-1-Mediated Endocytosis of EFF-1 Fusogen Controls Cell-Cell Fusion.
abstract: Cell-cell fusion plays essential roles during fertilization and organogenesis. Previous studies in C. elegans led to the identification of the eukaryotic fusion protein (EFF-1 fusogen), which has structural homology to class II viral fusogens. Transcriptional repression of EFF-1 ensures correct fusion fates, and overexpression of EFF-1 results in embryonic lethality. EFF-1 must be expressed on the surface of both fusing cells; however, little is known regarding how cells regulate EFF-1 surface exposure. Here, we report that EFF-1 is actively removed from the plasma membrane of epidermal cells by dynamin- and RAB-5-dependent endocytosis and accumulates in early endosomes. EFF-1 was transiently localized to apical domains of fusion-competent cells. Effective cell-cell fusion occurred only between pairs of cell membranes in which EFF-1 localized. Downregulation of dynamin or RAB-5 caused EFF-1 mislocalization to all apical membrane domains and excessive fusion. Thus, internalization of EFF-1 is a safety mechanism preventing excessive cell fusion.
authors: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel.
authors: Ksenia
authors: K
authors: Smurova
authors: Department of Biology, Technion-Israel Institute of Technology, Haifa 32000, Israel. Electronic address: podbilew@technion.ac.il.
authors: Benjamin
authors: B
authors: Podbilewicz
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002450:Cell Communication; D002459:Cell Fusion; D002462:Cell Membrane / Q000378:metabolism; D034284:Dynamin I / Q000235:genetics* / Q000378:metabolism; D004705:Endocytosis; D000078404:Epidermal Cells; D004817:Epidermis / Q000254:growth & development / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D008561:Membrane Fusion; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009024:Morphogenesis; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; C558452:Rab-5 protein, C elegans; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D034284:Dynamin I