Tenectin recruits integrin to stabilize bouton architecture and regulate vesicle release at the Drosophila neuromuscular junction
Abstract
Assembly, maintenance and function of synaptic junctions depend on extracellular matrix (ECM) proteins and their receptors. Here we report that Tenectin (Tnc), a Mucin-type protein with RGD motifs, is an ECM component required for the structural and functional integrity of synaptic specializations at the neuromuscular junction (NMJ) in Drosophila. Using genetics, biochemistry, electrophysiology, histology and electron microscopy, we show that Tnc is secreted from motor neurons and striated muscles and accumulates in the synaptic cleft. Tnc selectively recruits αPS2/βPS integrin at synaptic terminals, but only the cis Tnc/integrin complexes appear to be biologically active. These complexes have distinct pre- and postsynaptic functions, mediated at least in part through the local engagement of the spectrin-based membrane skeleton: the presynaptic complexes control neurotransmitter release, while postsynaptic complexes ensure the size and architectural integrity of synaptic boutons. Our study reveals an unprecedented role for integrin in the synaptic recruitment of spectrin-based membrane skeleton.
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All data generated or analysed during this study are included in the manuscript and supporting files.
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Funding
NIH Office of the Director (Z01 HD008914)
- Qi Wang
- Tae Hee Han
- Peter Nguyen
- Mihaela Serpe
NIH Office of the Director (Z01 HD008869)
- Qi Wang
- Tae Hee Han
- Peter Nguyen
- Mihaela Serpe
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Talila Volk, Weizmann Institute of Science, Israel
Version history
- Received: January 30, 2018
- Accepted: June 13, 2018
- Accepted Manuscript published: June 14, 2018 (version 1)
- Version of Record published: July 11, 2018 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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