Pan-neuronal knockdown of Ras GTPase-activating protein 1 alters Drosophila activity and sleep behavior.

Ras signaling pathways are involved in numerous cellular functions and, for this reason, are highly regulated. In addition to alterations in the Ras proteins themselves, defects in Ras regulatory proteins, such as GTPase-activating proteins (GAPs) and guanine nucleotide exchange factors (GEFs), may be relevant to disease development. Drosophila RasGAP1 is a protein with important physiological implications in flies due to its participation in the signaling of different pathways. In this work, the changes that occur in Drosophila behavior by reducing the pan-neuronal expression of RasGAP1 were investigated. Thus, RasGAP1 knockdown was found to cause a significant increase in total activity (p ≤ 0.001) and activity at 30 min (p ≤ 0.001). In contrast, total sleep duration (p ≤ 0.001), sleep within 30 min (p ≤ 0.001), and mean duration of sleep episodes (p ≤ 0.0001) were all reduced. Furthermore, circulating levels of glucose (p ≤ 0.05) and triacylglycerol (p ≤ 0.05) were found to be elevated. No significant changes were found in feeding behavior, food source selection, trehalose, or glycogen levels. All these results show new functions of RasGAP1 in Drosophila physiology and may also serve to explain some functions of human orthologs (RasGAP2/3 [RASA2/3]).