Transcriptional Feedback Links Lipid Synthesis to Synaptic Vesicle Pools in Drosophila Photoreceptors

Neuron. 2019 Feb 20;101(4):721-737.e4. doi: 10.1016/j.neuron.2019.01.015. Epub 2019 Feb 5.

Abstract

Neurons can maintain stable synaptic connections across adult life. However, the signals that regulate expression of synaptic proteins in the mature brain are incompletely understood. Here, we describe a transcriptional feedback loop between the biosynthesis and repertoire of specific phospholipids and the synaptic vesicle pool in adult Drosophila photoreceptors. Mutations that disrupt biosynthesis of a subset of phospholipids cause degeneration of the axon terminal and loss of synaptic vesicles. Although degeneration of the axon terminal is dependent on neural activity, activation of sterol regulatory element binding protein (SREBP) is both necessary and sufficient to cause synaptic vesicle loss. Our studies demonstrate that SREBP regulates synaptic vesicle levels by interacting with tetraspanins, critical organizers of membranous organelles. SREBP is an evolutionarily conserved regulator of lipid biosynthesis in non-neuronal cells; our studies reveal a surprising role for this feedback loop in maintaining synaptic vesicle pools in the adult brain.

Keywords: Drosophila; SREBP; lamina; lipid biosynthesis; neurodegeneration; photoreceptor; synaptic vesicle; visual system.

Publication types

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

MeSH terms

  • Animals
  • Drosophila melanogaster
  • Feedback, Physiological*
  • Phospholipids / biosynthesis*
  • Photoreceptor Cells, Invertebrate / metabolism*
  • Sterol Regulatory Element Binding Proteins / metabolism
  • Synaptic Vesicles / metabolism*
  • Tetraspanins / metabolism
  • Transcriptional Activation

Substances

  • Phospholipids
  • Sterol Regulatory Element Binding Proteins
  • Tetraspanins