Novel genetic link between the ATP-binding cassette subfamily A gene and hippo gene in Drosophila

Exp Cell Res. 2020 Jan 15;386(2):111733. doi: 10.1016/j.yexcr.2019.111733. Epub 2019 Nov 18.

Abstract

The pan-neuron-specific knockdown of dABCA, a Drosophila homologue of the human ATP binding cassette subfamily A member 13 gene, increases social space without affecting climbing ability and induces the early onset of evening activity in adult flies followed by relatively high activity throughout the day. Satellite bouton numbers in the presynaptic terminals of motor neurons are increased in dABCA knockdown flies. In the present study, we further characterized pan-neuron-specific dABCA knockdown flies and found that active zones in the presynaptic terminals of motor neurons increased, whereas learning abilities decreased in larvae. Genetic crossing experiments revealed that the hippo mutation enhanced the hyperactivity phenotype of adults, but suppressed the increased satellite bouton phenotype induced by the dABCA knockdown. Drosophila ABCA is predicted to transport lipid molecules and impair the asymmetric distribution of phospholipids across the plasma membrane, and these local changes are considered to be important for various cellular functions. The disruption of lipid homeostasis in central and peripheral nervous systems by the dABCA knockdown may affect the Hippo-related signaling pathway in order to induce the observed phenotypes.

Keywords: ATP-Binding cassette protein A; Activity monitoring; Autism spectrum disorder; Drosophila; Hippo gene; Neuron.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily A / deficiency
  • ATP Binding Cassette Transporter, Subfamily A / genetics*
  • Animals
  • Animals, Genetically Modified
  • Behavior, Animal / physiology
  • Biological Transport / genetics
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism
  • Female
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Homeostasis / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Larva / cytology
  • Larva / genetics
  • Larva / metabolism
  • Lipid Metabolism / genetics
  • Male
  • Motor Neurons / cytology
  • Motor Neurons / metabolism*
  • Mushroom Bodies / cytology
  • Mushroom Bodies / metabolism*
  • Mutation
  • Phenotype
  • Presynaptic Terminals / metabolism*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / metabolism
  • Signal Transduction

Substances

  • ATP Binding Cassette Transporter, Subfamily A
  • Drosophila Proteins
  • Intracellular Signaling Peptides and Proteins
  • Protein Serine-Threonine Kinases
  • hpo protein, Drosophila