Originally published as Genetics Published Articles Ahead of Print on March 17, 2006.

Genetics, Vol. 173, 177-187, May 2006, Copyright © 2006
doi:10.1534/genetics.106.057380

A Novel Gain-of-Function Mutant of the Cyclic GMP-Dependent Protein Kinase egl-4 Affects Multiple Physiological Processes in Caenorhabditis elegans

David M. Raizen*,{dagger},1, Kevin M. Cullison{ddagger}, Allan I. Pack§,{dagger} and Meera V. Sundaram{ddagger}

* Department of Neurology, {ddagger} Department of Genetics, § Department of Medicine and {dagger} Center for Sleep and Respiratory Neurobiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

1 Corresponding author: Center for Sleep, University of Pennsylvania School of Medicine, TRL 2122, 125 S. 31st St., Philadelphia, PA 19104.
E-mail: raizen{at}mail.med.upenn.edu

cGMP-dependent protein kinases are key intracellular transducers of cell signaling. We identified a novel dominant mutation in the C. elegans egl-4 cGMP-dependent protein kinase (PKG) and show that this mutation causes increased normal gene activity although it is associated with a reduced EGL-4 protein level. Prior phenotypic analyses of this gain-of-function mutant demonstrated a reduced longevity and a reduced feeding behavior when the animals were left unperturbed. We characterize several additional phenotypes caused by increased gene activity of egl-4. These phenotypes include a small body size, reduced locomotion in the presence of food, a pale intestine, increased intestinal fat storage, and a decreased propensity to form dauer larvae. The multiple phenotypes of egl-4 dominant mutants are consistent with an instructive signaling role of PKG to control many aspects of animal physiology. This is among the first reported gain-of-function mutations in this enzyme of central physiological importance. In a genetic screen we have identified extragenic suppressors of this gain-of-function mutant. Thus, this mutant promises to be a useful tool for identifying downstream targets of PKG.




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