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Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control
The AAA(+) NSF complex is responsible for SNARE complex disassembly both before and after membrane fusion. Loss of NSF function results in pronounced developmental and degenerative defects. In a genetic screen for sensory deficits in zebrafish, we identified a mutation in nsf, I209N, that impairs he...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524599/ https://www.ncbi.nlm.nih.gov/pubmed/37027300 http://dx.doi.org/10.1016/j.celrep.2023.112345 |
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author | Gao, Yan Khan, Yousuf A. Mo, Weike White, K. Ian Perkins, Matthew Pfuetzner, Richard A. Trapani, Josef G. Brunger, Axel T. Nicolson, Teresa |
author_facet | Gao, Yan Khan, Yousuf A. Mo, Weike White, K. Ian Perkins, Matthew Pfuetzner, Richard A. Trapani, Josef G. Brunger, Axel T. Nicolson, Teresa |
author_sort | Gao, Yan |
collection | PubMed |
description | The AAA(+) NSF complex is responsible for SNARE complex disassembly both before and after membrane fusion. Loss of NSF function results in pronounced developmental and degenerative defects. In a genetic screen for sensory deficits in zebrafish, we identified a mutation in nsf, I209N, that impairs hearing and balance in a dosage-dependent manner without accompanying defects in motility, myelination, and innervation. In vitro experiments demonstrate that while the I209N NSF protein recognizes SNARE complexes, the effects on disassembly are dependent upon the type of SNARE complex and I209N concentration. Higher levels of I209N protein produce a modest decrease in binary (syntaxin-SNAP-25) SNARE complex disassembly and residual ternary (syntaxin-1A-SNAP-25-synaptobrevin-2) disassembly, whereas at lower concentrations binary disassembly activity is strongly reduced and ternary disassembly activity is absent. Our study suggests that the differential effect on disassembly of SNARE complexes leads to selective effects on NSF-mediated membrane trafficking and auditory/vestibular function. |
format | Online Article Text |
id | pubmed-10524599 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
record_format | MEDLINE/PubMed |
spelling | pubmed-105245992023-09-27 Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control Gao, Yan Khan, Yousuf A. Mo, Weike White, K. Ian Perkins, Matthew Pfuetzner, Richard A. Trapani, Josef G. Brunger, Axel T. Nicolson, Teresa Cell Rep Article The AAA(+) NSF complex is responsible for SNARE complex disassembly both before and after membrane fusion. Loss of NSF function results in pronounced developmental and degenerative defects. In a genetic screen for sensory deficits in zebrafish, we identified a mutation in nsf, I209N, that impairs hearing and balance in a dosage-dependent manner without accompanying defects in motility, myelination, and innervation. In vitro experiments demonstrate that while the I209N NSF protein recognizes SNARE complexes, the effects on disassembly are dependent upon the type of SNARE complex and I209N concentration. Higher levels of I209N protein produce a modest decrease in binary (syntaxin-SNAP-25) SNARE complex disassembly and residual ternary (syntaxin-1A-SNAP-25-synaptobrevin-2) disassembly, whereas at lower concentrations binary disassembly activity is strongly reduced and ternary disassembly activity is absent. Our study suggests that the differential effect on disassembly of SNARE complexes leads to selective effects on NSF-mediated membrane trafficking and auditory/vestibular function. 2023-04-25 2023-04-05 /pmc/articles/PMC10524599/ /pubmed/37027300 http://dx.doi.org/10.1016/j.celrep.2023.112345 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License, which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use. |
spellingShingle | Article Gao, Yan Khan, Yousuf A. Mo, Weike White, K. Ian Perkins, Matthew Pfuetzner, Richard A. Trapani, Josef G. Brunger, Axel T. Nicolson, Teresa Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title | Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title_full | Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title_fullStr | Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title_full_unstemmed | Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title_short | Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control |
title_sort | sensory deficit screen identifies nsf mutation that differentially affects snare recycling and quality control |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10524599/ https://www.ncbi.nlm.nih.gov/pubmed/37027300 http://dx.doi.org/10.1016/j.celrep.2023.112345 |
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