Abstract
All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.
Highlights
The ability of an organism to sense nutrients in its environment is closely linked to survival (Lam, 2010)
The glutamatergic interneurons identified recently by us (Jayakumar et al, 2016), convey sensory signals received from cholinergic inputs to output peptidergic neurons. These glutamatergic neurons appear to function as integrators of multiple inputs that could include sensory and metabolic inputs from the fat-body (Koulakov et al, 2002). What makes these interneurons efficient integrators? One possibility is that calcium signaling through the IP3R allows such integration
It has been speculated that the IP3R in mouse hippocampal and cerebellar Purkinje neurons is required for activity-dependent plasticity in dendrites (Berridge, 1993; Nakamura et al, 1999; Hartmann and Konnerth, 2005; Taylor and Tovey, 2010)
Summary
The ability of an organism to sense nutrients in its environment is closely linked to survival (Lam, 2010). To survive and adapt to an ever-changing environment, organisms need to couple nutrient sensing mechanisms to signaling pathways that allow survival through conditions of nutrient stress. Such mechanisms regulate allocation of available nutrients for essential and non-essential processes, modulating growth and development. This regulation is dependent on consumption of appropriate levels of food, and different organisms have evolved nutrient sensing mechanisms for optimal food consumption (Gleason et al, 2007; Miyamoto et al, 2013; Chantranupong et al, 2015). An understanding of nutrient sensing mechanisms across phyla would provide insights into the regulation of metabolic decisions, of those related to survival under nutrient stress
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