USP5/Leon deubiquitinase confines postsynaptic growth by maintaining ubiquitin homeostasis through Ubiquilin
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.
Article and author information
Author details
Funding
Academia Sinica
- Chien-Hsiang Wang
- Yi-Chun Huang
- Pei-Yi Chen
- Ying-Ju Cheng
- Cheng-Ting Chien
Ministry of Science and Technology, Taiwan
- Chien-Hsiang Wang
- Yi-Chun Huang
- Pei-Yi Chen
- Ying-Ju Cheng
- Cheng-Ting Chien
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Hugo J Bellen, Baylor College of Medicine, United States
Version history
- Received: March 16, 2017
- Accepted: May 9, 2017
- Accepted Manuscript published: May 10, 2017 (version 1)
- Version of Record published: May 19, 2017 (version 2)
Copyright
© 2017, Wang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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