USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin

Elife. 2017 May 10;6:e26886. doi: 10.7554/eLife.26886.

Abstract

Synapse formation and growth are tightly controlled processes. How synaptic growth is terminated after reaching proper size remains unclear. Here, we show that Leon, the Drosophila USP5 deubiquitinase, controls postsynaptic growth. In leon mutants, postsynaptic specializations of neuromuscular junctions are dramatically expanded, including the subsynaptic reticulum, the postsynaptic density, and the glutamate receptor cluster. Expansion of these postsynaptic features is caused by a disruption of ubiquitin homeostasis with accumulation of free ubiquitin chains and ubiquitinated substrates in the leon mutant. Accumulation of Ubiquilin (Ubqn), the ubiquitin receptor whose human homolog ubiquilin 2 is associated with familial amyotrophic lateral sclerosis, also contributes to defects in postsynaptic growth and ubiquitin homeostasis. Importantly, accumulations of postsynaptic proteins cause different aspects of postsynaptic overgrowth in leon mutants. Thus, the deubiquitinase Leon maintains ubiquitin homeostasis and proper Ubqn levels, preventing postsynaptic proteins from accumulation to confine postsynaptic growth.

Keywords: D. melanogaster; USP5/Leon; Ubiquilin/Ubqn; developmental biology; free ubiquitin chains; neuroscience; postsynaptic growth; stem cells; ubiquitin homeostasis.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Homeostasis
  • Post-Synaptic Density / metabolism*
  • Receptors, Glutamate / metabolism*
  • Ubiquitin / metabolism*
  • Ubiquitin-Specific Proteases / metabolism*

Substances

  • Carrier Proteins
  • Cell Cycle Proteins
  • Drosophila Proteins
  • Receptors, Glutamate
  • Ubiquitin
  • Ubqn protein, Drosophila
  • USP5 protein, Drosophila
  • Ubiquitin-Specific Proteases

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.