dSTIM- and Ral/Exocyst-Mediated Synaptic Release from Pupal Dopaminergic Neurons Sustains Drosophila Flight

eNeuro. 2018 Jun 18;5(3):ENEURO.0455-17.2018. doi: 10.1523/ENEURO.0455-17.2018. eCollection May-Jun 2018.

Abstract

Manifestation of appropriate behavior in adult animals requires developmental mechanisms that help in the formation of correctly wired neural circuits. Flight circuit development in Drosophila requires store-operated calcium entry (SOCE) through the STIM/Orai pathway. SOCE-associated flight deficits in adult Drosophila derive extensively from regulation of gene expression in pupal neurons, and one such SOCE-regulated gene encodes the small GTPase Ral. The cellular mechanism by which Ral helps in maturation of the flight circuit was not understood. Here, we show that knockdown of components of a Ral effector, the exocyst complex, in pupal neurons also leads to reduced flight bout durations, and this phenotype derives primarily from dopaminergic neurons. Importantly, synaptic release from pupal dopaminergic neurons is abrogated upon knockdown of dSTIM, Ral, or exocyst components. Ral overexpression restores the diminished synaptic release of dStim knockdown neurons as well as flight deficits associated with dSTIM knockdown in dopaminergic neurons. These results identify Ral-mediated vesicular release as an effector mechanism of neuronal SOCE in pupal dopaminergic neurons with functional consequences on flight behavior.

Keywords: Exo84; Neural Circuit; SOCE; Synaptic Maturation.

Publication types

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

MeSH terms

  • Animals
  • Dopaminergic Neurons / metabolism*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Female
  • Flight, Animal*
  • Gene Knockdown Techniques
  • Larva / metabolism
  • Male
  • Stromal Interaction Molecule 1 / genetics
  • Stromal Interaction Molecule 1 / metabolism*
  • Synaptic Vesicles / metabolism*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*
  • ral GTP-Binding Proteins / genetics
  • ral GTP-Binding Proteins / metabolism*

Substances

  • Drosophila Proteins
  • Stim protein, Drosophila
  • Stromal Interaction Molecule 1
  • Vesicular Transport Proteins
  • ral GTP-Binding Proteins