Stac protein regulates release of neuropeptides

Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29914-29924. doi: 10.1073/pnas.2009224117. Epub 2020 Nov 9.

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 of stac genes 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 melanogaster contain a single stac gene, 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) in Drosophila motor neurons and this, in turn, controls the release of neuropeptides.

Keywords: Drosophila melanogaster; L-type voltage-gated calcium channel; neuropeptide; stac.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Behavior Observation Techniques
  • Behavior, Animal
  • Calcium Channels / metabolism*
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster
  • Female
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Intravital Microscopy
  • Larva
  • Male
  • Models, Animal
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Muscle, Skeletal / cytology
  • Muscle, Skeletal / metabolism
  • Neuromuscular Junction / cytology
  • Neuromuscular Junction / metabolism*
  • Neuropeptides / metabolism*
  • Optical Imaging
  • Patch-Clamp Techniques
  • Presynaptic Terminals / metabolism

Substances

  • Ca-alpha1D protein, Drosophila
  • Calcium Channels
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Neuropeptides
  • Stacl protein, Drosophila