C. elegans Enabled exhibits novel interactions with N-WASP, Abl, and cell-cell junctions.
Ena/VASP proteins are associated with cell-cell junctions in cultured mammalian cells [1] and Drosophila epithelia [2, 3], but they have only been extensively studied at the leading edges of migratory fibroblasts, where they modulate the protrusion of the leading edge [4]. They act by regulating actin-filament geometry, antagonizing the effects of actin-capping protein [5]. Embryos lacking the C. elegans Ena/VASP, UNC-34, display subtle defects in the leading edges of migrating epidermal cells but undergo normal epidermal morphogenesis. In contrast, embryos lacking both UNC-34 and the C. elegans N-WASP homolog have severe defects in epidermal morphogenesis, suggesting that they have parallel roles in coordinating cell behavior. GFP-tagged UNC-34 localizes to the leading edges of migrating epidermal cells, becoming redistributed to new junctions that form during epidermal-sheet sealing. Consistent with this, UNC-34 contributes to the formation of cadherin-based junctions. The junctional localization of UNC-34 is independent of proteins involved in Ena/VASP localization in other experimental systems; instead, junctional distribution depends upon the junctional protein AJM-1. We also show that Abelson tyrosine kinase, a major regulator of Enabled in Drosophila, is not required for UNC-34/Ena function in epithelia. Instead, our data suggest that Abelson kinase acts in parallel to UNC-34/Ena, antagonizing its function.
Sheffield
Mark
M
Program in Genetics, University of Wisconsin, 1117 West Johnson Street, Madison, Wisconsin 53706, USA.
Loveless
Timothy
T
Hardin
Jeff
J
Pettitt
Jonathan
J
D000818:Animals; D015820:Cadherins / Q000502:physiology; D017173:Caenorhabditis elegans / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D004817:Epidermis / Q000196:embryology; D007365:Intercellular Junctions / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016315:Proto-Oncogene Proteins c-abl / Q000502:physiology*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000502:physiology*
C441580:AJM-1 protein, C elegans; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D009419:Nerve Tissue Proteins; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C511070:unc-34 protein, C elegans; D016315:Proto-Oncogene Proteins c-abl