NonA and CPX Link the Circadian Clockwork to Locomotor Activity in Drosophila

Neuron. 2018 Aug 22;99(4):768-780.e3. doi: 10.1016/j.neuron.2018.07.001. Epub 2018 Jul 26.

Abstract

Drosophila NonA and its mammalian ortholog NONO are members of the Drosophila behavior and human splicing (DBHS) family. NONO also has a strong circadian connection: it associates with the circadian repressor protein PERIOD (PER) and contributes to circadian timekeeping. Here, we investigate NonA, which is required for proper levels of evening locomotor activity as well as a normal free-running period in Drosophila. NonA is associated with the positive transcription factor CLOCK/CYCLE (CLK/CYC), interacts directly with complexin (cpx) pre-mRNA, and upregulates gene expression, including the gene cpx. Downregulation of cpx expression in circadian neurons phenocopies NonA downregulation, whereas cpx overexpression rescues the nonA RNAi phenotypes, indicating that cpx is an important NonA target gene. As the cpx protein contributes to proper neurotransmitter and neuropeptide release in response to calcium, these results and others indicate that this control is important for the normal circadian regulation of locomotor activity.

Keywords: CLOCK; CPX; Drosophila; NonA; PDF; circadian rhythm; neuropeptide; neurotransmitter; vesicle release.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / biosynthesis*
  • Adaptor Proteins, Vesicular Transport / genetics
  • Animals
  • Animals, Genetically Modified
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Drosophila
  • Drosophila Proteins / biosynthesis*
  • Drosophila Proteins / genetics
  • Locomotion / physiology*
  • Male
  • Nerve Tissue Proteins / biosynthesis*
  • Nerve Tissue Proteins / genetics
  • Nuclear Proteins / biosynthesis*
  • Nuclear Proteins / genetics

Substances

  • Adaptor Proteins, Vesicular Transport
  • Drosophila Proteins
  • NONA protein, Drosophila
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • cpx protein, Drosophila