title: Essential kinase-independent role of a Fer-like non-receptor tyrosine kinase in Caenorhabditis elegans morphogenesis.
abstract: Morphogenesis requires coordination of cell surface activity and cytoskeletal architecture. During the initial stage of morphogenesis in Caenorhabditis elegans, the concerted movement of surface epithelial cells results in enclosure of the embryo by the epidermis. We report that Fer-related kinase-1 (FRK-1), an ortholog of the mammalian non-receptor tyrosine kinase Fer, is necessary for embryonic enclosure and morphogenesis in C. elegans. Expression of FRK-1 in epidermal cells is sufficient to rescue a chromosomal deficiency that removes the frk-1 locus, demonstrating its autonomous requirement in the epidermis. The essential function of FRK-1 is independent of its kinase domain, suggesting a non-enzymatic role in morphogenesis. Localization of FRK-1 to the plasma membrane requires beta-catenin, but not cadherin or alpha-catenin, and muscle-expressed beta-integrin is non-autonomously required for this localization; in the absence of these components FRK-1 becomes nuclear. Mouse FerT rescues the morphogenetic defects of frk-1 mutants and expression of FRK-1 in mammalian cells results in loss of adhesion, implying a conserved function for FRK-1/FerT in cell adhesion and morphogenesis. Thus, FRK-1 performs a kinase-independent function in differentiation and morphogenesis of the C. elegans epidermis during embryogenesis.
authors.affiliation: Neuroscience Research Institute and Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA 93106, USA.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Putzke
authors.forename: Sherry T
authors.initials: ST
authors.lastname: Hikita
authors.forename: Dennis O
authors.initials: DO
authors.lastname: Clegg
authors.forename: Joel H
authors.initials: JH
authors.lastname: Rothman
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology* / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004817:Epidermis / Q000196:embryology*; D006801:Humans; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; C106933:FER-1 protein, C elegans; D008565:Membrane Proteins; D009687:Nuclear Proteins; C052602:proto-oncogene protein c-fes-fps; D011505:Protein-Tyrosine Kinases; C503592:FRK-1 protein, C elegans