Mayday sustains trans-synaptic BMP signaling required for synaptic maintenance with age

Elife. 2021 Mar 5:10:e54932. doi: 10.7554/eLife.54932.

Abstract

Maintaining synaptic structure and function over time is vital for overall nervous system function and survival. The processes that underly synaptic development are well understood. However, the mechanisms responsible for sustaining synapses throughout the lifespan of an organism are poorly understood. Here, we demonstrate that a previously uncharacterized gene, CG31475, regulates synaptic maintenance in adult Drosophila NMJs. We named CG31475 mayday due to the progressive loss of flight ability and synapse architecture with age. Mayday is functionally homologous to the human protein Cab45, which sorts secretory cargo from the Trans Golgi Network (TGN). We find that Mayday is required to maintain trans-synaptic BMP signaling at adult NMJs in order to sustain proper synaptic structure and function. Finally, we show that mutations in mayday result in the loss of both presynaptic motor neurons as well as postsynaptic muscles, highlighting the importance of maintaining synaptic integrity for cell viability.

Keywords: D. melanogaster; Drosophila; flight; genetics; genomics; neuromuscular junction; neuroscience; synapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aging
  • Animals
  • Animals, Genetically Modified
  • Bone Morphogenetic Proteins / metabolism*
  • Cell Communication
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / physiology
  • Flight, Animal / physiology*
  • Motor Neurons / physiology
  • Muscles / physiology
  • Mutation
  • Signal Transduction
  • Synapses / physiology*

Substances

  • Bone Morphogenetic Proteins
  • Drosophila Proteins