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Essential kinase-independent role of a Fer-like non-receptor tyrosine kinase in Caenorhabditis elegans morphogenesis. Export

Development, Vol. 132 (2005), pp. 3185-3195.

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article caenorhabditis_elegans celegans c_elegans elegans elt-1 emb-9 f01g125 frk-1 hmp-1 hmp-2 hmr-1 jac-1 k04h41 k05c46 let-2 nematode pat-3 r13h44 t04b22 w02b91 w09c21 wormbase y105c5b21 zk10582

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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 nonautonomously 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


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