KIN-29 SIK SIGNALING THE THEREGULATION OF FOOD-RELATED BEHAVIORS & DEVELOPMENT

University Of Nevada Reno, Reno NV

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The availability and quality of food fluctuates over time in an animal's environment. When food is scarce, an animal must undergo changes in its behavior, metabolism and physiology to promote survival. An animal must also regulate its feeding habits depending on nutritional status in order to maintain physiological homeostasis. Salt-inducing kinases (SIKs) are important regulators of energy homeostasis, and feeding/fasting responses in mammals. We previously found that KIN-29, the C. elegans homolog of SIK, modulates chemoreceptor (CR) gene expression, feeding behaviors and body size. We believe that CR gene modulation underlies, at least in part, the ability of animals to correctly transduce food-derived signals to modulate feeding and body-size. To further dissect the KIN-29 signaling pathways by which food signals are integrated to modulate behavior and development, we are taking three parallel strategies to define new targets of KIN-29. In the first, we are determining the gene expression profiles of specific sensory neurons using next-generation sequencing coupled to a mRNA-tagging approach. Preliminary results using microarrays indicate that a large subset of genes predicted to function in transcriptional regulation and phosphorylation events are up- and down-regulated, respectively, in wild-type and kin-29 mutants in chemosensory neurons. Secondly, we are examining a KIN-29-dependent CR gene whose expression in the ADL chemosensory neurons is acutely altered by the presence and absence of food in adult animals. We will take advantage of these observations to identify the components and neurons by which food signals alter CR gene expression using genetic screens. Finally, we are examining the function the single C. elegans homolog of CRTC/TORC, which is phosphorylated by SIK family members and is an important regulator of metabolism in mammals and flies. Together these experiments will provide a detailed understanding of the remarkably complex effects of food on animal development and behavior.