Stac protein regulates release of neuropeptides

Author:

Hsu I-UenORCID,Linsley Jeremy W.ORCID,Zhang XiaoliORCID,Varineau Jade E.,Berkhoudt Drew A.,Reid Lilly E.ORCID,Lum Miranda C.,Orzel Allison M.,Leflein Ari,Xu HaoxingORCID,Collins Catherine A.ORCID,Hume Richard I.ORCID,Levitan Edwin S.ORCID,Kuwada John Y.

Abstract

Neuropeptides are important for regulating numerous neural functions and behaviors. Release of neuropeptides requires long-lasting, high levels of cytosolic Ca2+. However, the molecular regulation of neuropeptide release remains to be clarified. Recently, Stac3 was identified as a key regulator of L-type Ca2+channels (CaChs) and excitation–contraction coupling in vertebrate skeletal muscles. There is a small family ofstacgenes in vertebrates with other members expressed by subsets of neurons in the central nervous system. The function of neural Stac proteins, however, is poorly understood.Drosophila melanogastercontain a singlestacgene,Dstac, which is expressed by muscles and a subset of neurons, including neuropeptide-expressing motor neurons. Here, genetic manipulations, coupled with immunolabeling, Ca2+imaging, electrophysiology, and behavioral analysis, revealed that Dstac regulates L-type CaChs (Dmca1D) inDrosophilamotor neurons and this, in turn, controls the release of neuropeptides.

Funder

HHS | NIH | National Institute of Arthritis and Musculoskeletal and Skin Diseases

HHS | NIH | National Institute of Neurological Disorders and Stroke

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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