The EGL-4 PKG Acts with KIN-29 Salt-Inducible Kinase and Protein Kinase A to Regulate Chemoreceptor Gene Expression and Sensory Behaviors in Caenorhabditis Elegans
van der Linden, Alexander M., Wiener, Scott, You, Young-jai, Kim, Kyuhyung, Avery, Leon, Sengupta, Piali, Genetics
The regulation of chemoreceptor (CR) gene expression by environmental signals and internal cues may contribute to the modulation of multiple physiological processes and behavior in Caenorhabditis elegans. We previously showed that KIN-29, a homolog of salt-inducible kinase, acts in sensory neurons to regulate the expression of a subset of CR genes, as well as sensory behaviors. Here we show that the cGMP-dependent protein kinase EGL-4 acts partly in parallel with KIN-29 to regulate CR gene expression. Sensory inputs inhibit both EGL-4 and KIN-29 functions, and KIN-29 function is inhibited in turn by cAMP-dependent protein kinase (PKA) activation. EGL-4 and KIN-29 regulate CR gene expression by antagonizing the gene repression functions of the class II HDAC HDA-4 and the MEF-2 transcription factor, and KIN-29, EGL-4, and PKA target distinct residues in HDA-4 to regulate its function and subcellular localization. While KIN-29 acts primarily via MEF-2/HDA-4 to regulate additional sensory signal-regulated physiological processes and behaviors, EGL-4 acts via both MEF-2-dependent and -independent pathways. Our results suggest that integration of complex sensory inputs via multiple signaling pathways allows animals to precisely regulate sensory gene expression, thereby appropriately modulating physiology and behavior.
CHEMOSENSORY signals regulate multiple aspects of animal development, physiology, and behavior. For example, chemical cues permit successful foraging in social insects, regulate sexual maturation in rodents, and provide information about reproductive status to potential mates (Dulac and Torello 2003; Jackson and Ratnieks 2006). Food-derived chemosensory cues signal palatability, are critical for the regulation of appetitive and feeding behaviors, and have been shown to regulate life span in both Drosophila and Caenorhabditis elegans (Apfeld and Kenyon 1999; Schwartz et al. 2000; Alcedo and Kenyon 2004; Rolls 2005; Libert et al. 2007). It is therefore essential that animals precisely regulate their ability to sense and respond to environmental chemicals.
C. elegans provides an excellent system in which to explore the neuronal and molecular mechanisms by which animals sense and respond to chemical cues. Sensory signals from food regulate nearly all aspects of C. elegans physiology, behavior, and development, including the regulation of entry/exit from the alternate dauer developmental stage, male mating, body size, locomotion, egg laying, longevity, and fat storage (Golden and Riddle 1984a,b; Apfeld and Kenyon 1999; Sawin et al. 2000;Waggoner et al. 2000; Fujiwara et al. 2002; Lanjuin and Sengupta 2002;Mak et al. 2006; Gruninger et al. 2008). As in other animals, chemosensory behaviors are plastic and are regulated by prior experience and external and internal cues (Sawin et al. 2000; Gray et al. 2005; Zhang et al. 2005; Shtonda and Avery 2006). Chemicals are sensed by a small number of chemosensory neurons, each of which expresses multiple candidate seven transmembrane domain chemoreceptors (CRs) and other signaling proteins (Bargmann 2006). The expression of each CR gene is regulated in a complex manner by multiple developmental and environmental cues, suggesting that regulated expression of CR gene subsets may partly underlie the modulation of chemosensory behaviors in C. elegans (Peckol et al. 2001; Lanjuin and Sengupta 2002; Nolan et al. 2002; van der Linden et al. 2007).
We previously showed that the KIN-29 Ser/Thr kinase acts in C. elegans sensory neurons to regulate chemosensory signal-dependent development and behavior (Lanjuin and Sengupta 2002). kin-29 mutants are small and exhibit deregulated entry into the dauer developmental stage, as well as altered food-regulated foraging behaviors (Lanjuin and Sengupta 2002; Maduzia et al. 2005). All mutant phenotypes can be rescued by expression of kin-29 only in sensory neurons (Lanjuin and Sengupta 2002). We found that KIN-29 regulates the expression of a subset of CR genes in multiple chemosensory neuron types, suggesting that altered expression of CR genes may lead to the inability of kin-29 mutants to correctly sense and transduce food signals (Lanjuin and Sengupta 2002). …