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Originally published as Genetics Published Articles Ahead of Print on August 9, 2008.
Genetics, Vol. 179, 1957-1971, August 2008, Copyright © 2008
doi:10.1534/genetics.108.088963
The Arp2/3 Activators WAVE and WASP Have Distinct Genetic Interactions With Rac GTPases in Caenorhabditis elegans Axon Guidance
M. Afaq Shakir*,1,2,
Ke Jiang*,1,3,
Eric C. Struckhoff*,
Rafael S. Demarco*,
Falshruti B. Patel
,
Martha C. Soto
and
Erik A. Lundquist*,4
* Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas 66045-7534 and
Department of Pathology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854
4 Corresponding author: Department of Molecular Biosciences, 1200 Sunnyside Ave., 5049 Haworth Hall, University of Kansas, Lawrence, KS 66045.
E-mail: erikl{at}ku.edu
In the developing nervous system, axons are guided to their targets by the growth cone. Lamellipodial and filopodial protrusions from the growth cone underlie motility and guidance. Many molecules that control lamellipodia and filopodia formation, actin organization, and axon guidance have been identified, but it remains unclear how these molecules act together to control these events. Experiments are described here that indicate that, in Caenorhabditis elegans, two WH2-domain-containing activators of the Arp2/3 complex, WVE-1/WAVE and WSP-1/WASP, act redundantly in axon guidance and that GEX-2/Sra-1 and GEX-3/Kette, molecules that control WAVE activity, might act in both pathways. WAVE activity is controlled by Rac GTPases, and data are presented here that suggest WVE-1/WAVE and CED-10/Rac act in parallel to a pathway containing WSP-1/WASP and MIG-2/RhoG. Furthermore, results here show that the CED-10/WVE-1 and MIG-2/WSP-1 pathways act in parallel to two other molecules known to control lamellipodia and filopodia and actin organization, UNC-115/abLIM and UNC-34/Enabled. These results indicate that at least three actin-modulating pathways act in parallel to control actin dynamics and lamellipodia and filopodia formation during axon guidance (WASP–WAVE, UNC-115/abLIM, and UNC-34/Enabled).
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Genetics 2008 179: NP.
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