Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control
Summary: 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 imp...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112472300356X |
| _version_ | 1797850944795312128 |
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| author | Yan Gao Yousuf A. Khan Weike Mo K. Ian White Matthew Perkins Richard A. Pfuetzner Josef G. Trapani Axel T. Brunger Teresa Nicolson |
| author_facet | Yan Gao Yousuf A. Khan Weike Mo K. Ian White Matthew Perkins Richard A. Pfuetzner Josef G. Trapani Axel T. Brunger Teresa Nicolson |
| author_sort | Yan Gao |
| collection | DOAJ |
| description | Summary: 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. |
| first_indexed | 2024-04-09T19:09:49Z |
| format | Article |
| id | doaj.art-fa469058d265459a95ab589acda03f97 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-09T19:09:49Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-fa469058d265459a95ab589acda03f972023-04-07T06:50:11ZengElsevierCell Reports2211-12472023-04-01424112345Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality controlYan Gao0Yousuf A. Khan1Weike Mo2K. Ian White3Matthew Perkins4Richard A. Pfuetzner5Josef G. Trapani6Axel T. Brunger7Teresa Nicolson8Department of Otolaryngology, Head and Neck Surgery, Stanford Medical School, 300 Pasteur Drive, Stanford, CA 94303, USADepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USAGraduate Program Biomedical Sciences, Oregon Hearing Research Center and Vollum Institute, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USADepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USADepartment of Biology and Neuroscience Program, Amherst College, Amherst, MA 01002, USADepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USADepartment of Biology and Neuroscience Program, Amherst College, Amherst, MA 01002, USADepartment of Molecular and Cellular Physiology, Stanford University, Stanford, CA, USA; Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA; Department of Structural Biology, Stanford University, Stanford, CA, USA; Department of Photon Science, Stanford University, Stanford, CA, USA; Howard Hughes Medical Institute, Stanford University, Stanford, CA, USADepartment of Otolaryngology, Head and Neck Surgery, Stanford Medical School, 300 Pasteur Drive, Stanford, CA 94303, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S221112472300356XCP: Neuroscience |
| spellingShingle | Yan Gao Yousuf A. Khan Weike Mo K. Ian White Matthew Perkins Richard A. Pfuetzner Josef G. Trapani Axel T. Brunger Teresa Nicolson Sensory deficit screen identifies nsf mutation that differentially affects SNARE recycling and quality control Cell Reports CP: Neuroscience |
| 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 | CP: Neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S221112472300356X |
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