Fusogenic activity of EFF-1 is regulated via dynamic localization in fusing somatic cells of C. elegans.
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.
del Campo
Jacob J
JJ
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
Opoku-Serebuoh
Eugene
E
Isaacson
Ariel B
AB
Scranton
Victoria L
VL
Tucker
Morgan
M
Han
Min
M
Mohler
William A
WA
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
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; C470734:EFF-1 protein, C elegans; D008562:Membrane Glycoproteins; D049452:Green Fluorescent Proteins