A RHO GTPase-mediated pathway is required during P cell migration in Caenorhabditis elegans
- †Howard Hughes Medical Institute, Department of Molecular Cell and Developmental Biology, University of Colorado, Boulder, CO 80309-0347; and ‡Shionogi and Co., Osaka 553-0002 Japan
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Communicated by William B. Wood, University of Colorado, Boulder, CO (received for review August 26, 2001)
Abstract
The Rho family of guanine triphosphate hydrolases controls various cellular processes, including cell migration. We describe here the demonstration of a role for a RhoA GTPase homologue during cell migration in Caenorhabditis elegans. We show that eliminating or reducing rho-1 gene function by using a dominant-negative transgene or dsRNA interference results in a severe defect in migration of hypodermal P cells to a ventral position. Biochemical and genetic data also suggest that unc-73, which encodes a Trio-like guanine nucleotide exchange factor, may act as an activator of rho-1 in the migration process. Mutations in let-502 ROCK, a homologue of a RhoA effector in mammals, also cause defects in P cell migration, suggesting that it may be one of several effectors acting downstream of rho-1 during P cell migration. Finally, we provide evidence to support the idea that other small Rac subfamily small GTPases act redundantly and in parallel to RHO-1 in this specific cell migration event.
Footnotes
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↵ * A.G.S., S.O., and C.J.M. contributed equally to this work.
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↵ § Present address: 227D R.M. Bock Labs, University of Wisconsin, Madison, WI 53706.
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↵ ¶ To whom reprint requests should be addressed. E-mail: mhan{at}coloradoedu.
- Abbreviations:
- GEF,
- guanine nucleotide exchange factor;
- DH,
- Dbl homology;
- PH,
- pleckstrin homology;
- MCS,
- multiple cloning site;
- GFP,
- green fluorescent protein;
- dsRNA,
- double-stranded RNA;
- DAPI,
- 4′,6-diamidino-2-phenylindole
- Copyright © 2001, The National Academy of Sciences
