title: Fusogenic activity of EFF-1 is regulated via dynamic localization in fusing somatic cells of C. elegans.
abstract: BACKGROUND
  Many animal tissues form via fusion of cells. Yet in all instances of developmental cell fusion, the mechanism underlying fusion of plasma membranes remains poorly understood. EFF-1 is required for most somatic cell fusions in C. elegans, and misexpressed EFF-1 alters the normal pattern of fusing hypodermal cells. However, the autonomous activity of EFF-1, the rules governing its specificity, and the mechanism of its action have not been examined.
  
  
  RESULTS
  We show that EFF-1 acts as a cellular fusogen, capable of inducing fusion of virtually any somatic cells in C. elegans, yet targeted precisely to fusion-fated contacts during normal development. Misexpression of EFF-1 in early embryos causes fusion among groups of cells composed entirely of nonfusion-fated members. Measurements of cytoplasm diffusion in induced fusion events show that ectopic EFF-1 expression produces fusion pores similar to those in normal fusion events. GFP-labeled EFF-1 is specifically targeted to fusion-competent cell contacts via reciprocal localization to the touching membranes of EFF-1-expressing cells. EFF-1 function is also governed by intercellular barriers that prohibit cell fusion between distinct tissues. Analysis of mutant versions of EFF-1 indicates a novel mode of fusogenicity, employing neither a phospholipase active site nor hydrophobic fusion-peptide acting solely in pore formation.
  
  
  CONCLUSIONS
  EFF-1 can confer potent fusogenic activity to nonfusing cell types. However, it is normally targeted only to fusion-fated cell borders via mutual interaction between EFF-1-expressing cells and relocalization to the plasma membrane. Because EFF-1 appears evolutionarily unique to nematodes, multiple mechanisms may have evolved for controlled plasma-membrane fusion in development.
authors.affiliation: Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: del Campo
authors.forename: Eugene
authors.initials: E
authors.lastname: Opoku-Serebuoh
authors.forename: Ariel B
authors.initials: AB
authors.lastname: Isaacson
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Scranton
authors.forename: Morgan
authors.initials: M
authors.lastname: Tucker
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: William A
authors.initials: WA
authors.lastname: Mohler
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology; D019295:Computational Biology; D017931:DNA Primers; D040461:Gene Components; D018507:Gene Expression Regulation, Developmental; D049452:Green Fluorescent Proteins; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D016297:Mutagenesis, Site-Directed; D009154:Mutation / Q000235:genetics; D010957:Plasmids / Q000235:genetics; D019076:Transgenes / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; D049452:Green Fluorescent Proteins