Abstract
Ror kinases are a family of orphan receptors with tyrosine kinase activity that are related to muscle specific kinase (MuSK), a receptor tyrosine kinase that assembles acetylcholine receptors at the neuromuscular junction1,2. Although the functions of Ror kinases are unknown, similarities between Ror and MuSK kinases have led to speculation that Ror kinases regulate synaptic development. Here we show that the Caenorhabditis elegans gene cam-1 encodes a member of the Ror kinase family that guides migrating cells and orients the polarity of asymmetric cell divisions and axon outgrowth. We find that tyrosine kinase activity is required for some of the functions of CAM-1, but not for its role in cell migration. CAM-1 is expressed in cells that require its function, and acts cell autonomously in migrating neurons. Overexpression and loss of cam-1 function result in reciprocal cell-migration phenotypes, indicating that levels of CAM-1 influence the final positions of migrating cells. Our results raise the possibility that Ror kinases regulate cell motility and asymmetric cell division in organisms as diverse as nematodes and mammals.
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Acknowledgements
We thank B. Meyer and J. Kaplan for critical reading of this manuscript; K.Kozminski, for microscopy assistance; Y. Kohara for cDNA clones; O. Hobert for the ttx-3-gfp transgene; and C. Walczak for inspiration. This work was supported by a grant from NIH to G.G. and by postdoctoral fellowships from the NIH and the Breast Cancer Research Program of the US Army Medical and Materiel Command to W.C.F.
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Forrester, W., Dell, M., Perens, E. et al. A C. elegans Ror receptor tyrosine kinase regulates cell motility and asymmetric cell division. Nature 400, 881–885 (1999). https://doi.org/10.1038/23722
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DOI: https://doi.org/10.1038/23722
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