The F-BAR domain of SRGP-1 facilitates cell-cell adhesion during C. elegans morphogenesis.
Robust cell-cell adhesion is critical for tissue integrity and morphogenesis, yet little is known about the molecular mechanisms controlling cell-cell junction architecture and strength. We discovered that SRGP-1 is a novel component of cell-cell junctions in Caenorhabditis elegans, localizing via its F-BAR (Bin1, Amphiphysin, and RVS167) domain and a flanking 200-amino acid sequence. SRGP-1 activity promotes an increase in membrane dynamics at nascent cell-cell contacts and the rapid formation of new junctions; in addition, srgp-1 loss of function is lethal in embryos with compromised cadherin-catenin complexes. Conversely, excess SRGP-1 activity leads to outward bending and projections of junctions. The C-terminal half of SRGP-1 interacts with the N-terminal F-BAR domain and negatively regulates its activity. Significantly, in vivo structure-function analysis establishes a role for the F-BAR domain in promoting rapid and robust cell adhesion during embryonic closure events, independent of the Rho guanosine triphosphatase-activating protein domain. These studies establish a new role for this conserved protein family in modulating cell-cell adhesion.
Department of Zoology, University of Wisconsin-Madison, Madison, WI 53706, USA. biezbr@nus.edu.sg
Ronen
R
Zaidel-Bar
Michael J
MJ
Joyce
Allison M
AM
Lynch
Kristen
K
Witte
Anjon
A
Audhya
Jeff
J
Hardin
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000378:metabolism*; D009024:Morphogenesis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D019076:Transgenes; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; D011993:Recombinant Fusion Proteins; D051178:alpha Catenin; D051176:beta Catenin