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“Neuropeptides required for Drosophila development under nutritional stress are regulated by the ER-Ca2+ sensor STIM”

View ORCID ProfileMegha, View ORCID ProfileChristian Wegener, View ORCID ProfileGaiti Hasan
doi: https://doi.org/10.1101/386649
Megha
National Centre For Biological Sciences, Tata Institute for Fundamental Research, Bellary Road, Bangalore 560065
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  • For correspondence: meghaphd@ncbs.res.in
Christian Wegener
Department of Neurobiology and Genetics, University of Wurzburg, Am Hubland, 97074 Wurzburg
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Gaiti Hasan
National Centre For Biological Sciences, Tata Institute for Fundamental Research, Bellary Road, Bangalore 560065
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Abstract

Significance Elevation of cytosolic Ca2+ is required for the release of neuropeptides from specialised secretory neurons called neuroendocrine cells. Release of Ca2+ stored in the ER, which further triggers Ca2+ entry from the extracellular milieu is called Store-operated Ca2+ entry (SOCE). STIM, an ER protein, is a key regulator of SOCE and its contribution to neuroendocrine cell functioning is not well studied. Using Drosophila larval development under nutrient restriction as a paradigm, we identified two SOCE regulated neuropeptides, Corazonin and short Neuropeptide F. Reducing STIM alters the level of these neuropeptides in the fed as well as nutrient restricted condition. This study suggests that STIM-triggered SOCE may regulate the release of neuropeptides whose activity ultimately regulates adaptation to nutritional stress.

Abstract Cytosolic Ca2+ levels are tightly regulated by the sequestration of Ca2+ within the endoplasmic reticulum (ER). Loss of ER Ca2+ is sensed by STromal Interacting Molecule (STIM), whose translocation to the plasma membrane triggers Store Operated Ca2+ Entry (SOCE), and a subsequent rise in cytosolic Ca2+. Relatively little is known about SOCE’s contribution to neuroendocrine cells; a neuronal sub-type that specializes in the secretion of neuropeptides (NPs) which ultimately regulate animal physiology and behavior. To investigate how SOCE regulates NPs, Drosophila development under nutrient restriction (NR) was used as the biological context. Genetic experiments identified the requirement of two SOCE-regulated NPs-corazonin (Crz) and short neuropeptide F (sNPF) - for the development of NR larvae to pupae and finally, adulthood. Overexpression of SOCE regulators was sufficient to rescue the development of NR larvae with reduced sNPF or Crz levels. To facilitate cellular investigations, a restricted set of neurons that produce sNPF and Crz, and are activated by NR, were identified. Immunohistochemistry on these neurons and mass spectrometric measurements of their projections showed that dSTIM regulates Crz and sNPF levels at steady state and in response to NR, likely by modulating their release. Genetically increasing neuronal output, in the background of reduced dSTIM, robustly rescued development of NR larvae. Because NP action fundamentally underpins how animals adapt to stimuli, regulation of NPs by STIM triggered SOCE is likely to be important. In situations where SOCE is altered, such as neurodegenerative diseases, this regulation may contribute to disease manifestation and progression.

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Posted August 07, 2018.
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“Neuropeptides required for Drosophila development under nutritional stress are regulated by the ER-Ca2+ sensor STIM”
Megha, Christian Wegener, Gaiti Hasan
bioRxiv 386649; doi: https://doi.org/10.1101/386649
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“Neuropeptides required for Drosophila development under nutritional stress are regulated by the ER-Ca2+ sensor STIM”
Megha, Christian Wegener, Gaiti Hasan
bioRxiv 386649; doi: https://doi.org/10.1101/386649

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