The C. elegans zonula occludens ortholog cooperates with the cadherin complex to recruit actin during morphogenesis.
The dramatic cell-shape changes necessary to form a multicellular organism require cell-cell junctions to be both pliable and strong. The zonula occludens (ZO) subfamily of membrane-associated guanylate kinases (MAGUKs) are scaffolding molecules thought to regulate cell-cell adhesion [1-3], but there is little known about their roles in vivo. To elucidate the functional role of ZO proteins in a living embryo, we have characterized the sole C. elegans ZO family member, ZOO-1. ZOO-1 localizes with the cadherin-catenin complex during development, and its junctional recruitment requires the transmembrane proteins HMR-1/E-cadherin and VAB-9/claudin, but surprisingly, not HMP-1/alpha-catenin or HMP-2/beta-catenin. zoo-1 knockdown results in lethality during elongation, resulting in the rupture of epidermal cell-cell junctions under stress and failure of epidermal sheet sealing at the ventral midline. Consistent with a role in recruiting actin to the junction in parallel to the cadherin-catenin complex, zoo-1 loss of function reduces the dynamic recruitment of actin to junctions and enhances the severity of actin filament defects in hypomorphic alleles of hmp-1 and hmp-2. These results show that ZOO-1 cooperates with the cadherin-catenin complex to dynamically regulate strong junctional anchorage to the actin cytoskeleton during morphogenesis.
Lockwood
Christina
C
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, 1117 W. Johnson Street, Madison, WI 53706, USA.
Zaidel-Bar
Ronen
R
Hardin
Jeff
J
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000166:cytology / Q000196:embryology / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics / Q000494:pharmacology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051528:Guanylate Kinases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D009024:Morphogenesis / Q000502:physiology*; D034622:RNA Interference; D019108:Tight Junctions / Q000378:metabolism*; D051178:alpha Catenin / Q000378:metabolism
D000199:Actins; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C442473:HMP-2 protein, C elegans; D008565:Membrane Proteins; C476324:VAB-9 protein, C elegans; C533190:ZOO-1 protein, C elegans; D051178:alpha Catenin; C450060:hmr-1 protein, C elegans; D051528:Guanylate Kinases