A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans
Synaptic vesicles (SV) store various neurotransmitters that are released at the synapse. The molecular mechanisms of biogenesis, exocytosis, and endocytosis for SV, however, remain largely elusive. In this study, using Complex Object Parametric Analysis and Sorter (COPAS) to monitor the fluorescence...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-05-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00141/full |
| _version_ | 1819062876914057216 |
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| author | Mei Han Mei Han Mei Han Wenjuan Zou Hao Chang Hao Chang Yong Yu Haining Zhang Shitian Li Hankui Cheng Guifeng Wei Yan Chen Valerie Reinke Tao Xu Lijun Kang |
| author_facet | Mei Han Mei Han Mei Han Wenjuan Zou Hao Chang Hao Chang Yong Yu Haining Zhang Shitian Li Hankui Cheng Guifeng Wei Yan Chen Valerie Reinke Tao Xu Lijun Kang |
| author_sort | Mei Han |
| collection | DOAJ |
| description | Synaptic vesicles (SV) store various neurotransmitters that are released at the synapse. The molecular mechanisms of biogenesis, exocytosis, and endocytosis for SV, however, remain largely elusive. In this study, using Complex Object Parametric Analysis and Sorter (COPAS) to monitor the fluorescence of synapto-pHluorin (SpH), we performed a whole-genome RNAi screen in C. elegans to identify novel genetic modulators in SV cycling. One hundred seventy six genes that up-regulating SpH fluorescence and 96 genes that down-regulating SpH fluorescence were identified after multi-round screen. Among these genes, B0035.1 (bugz-1) encodes ortholog of mammalian C2H2 zinc-finger protein BuGZ/ZNF207, which is a spindle assembly checkpoint protein essential for mitosis in human cells. Combining electrophysiology, imaging and behavioral assays, we reveal that depletion of BuGZ-1 results in defects in locomotion. We further demonstrate that BuGZ-1 promotes SV recycling by regulating the expression levels of endocytosis-related genes such as rab11.1. Therefore, we have identified a bunch of potential genetic modulators in SV cycling, and revealed an unexpected role of BuGZ-1 in regulating synaptic transmission. |
| first_indexed | 2024-12-21T15:05:45Z |
| format | Article |
| id | doaj.art-6cabb0244f464ce896acd368b2d19db3 |
| institution | Directory Open Access Journal |
| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-21T15:05:45Z |
| publishDate | 2017-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-6cabb0244f464ce896acd368b2d19db32022-12-21T18:59:26ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992017-05-011010.3389/fnmol.2017.00141263578A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegansMei Han0Mei Han1Mei Han2Wenjuan Zou3Hao Chang4Hao Chang5Yong Yu6Haining Zhang7Shitian Li8Hankui Cheng9Guifeng Wei10Yan Chen11Valerie Reinke12Tao Xu13Lijun Kang14Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of MedicineHangzhou, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaDepartment of Genetics, Yale University School of MedicineNew Haven, CT, USAKey Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of MedicineHangzhou, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaDepartment of Genetics, Yale University School of MedicineNew Haven, CT, USANational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaKey Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of MedicineHangzhou, ChinaKey Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of MedicineHangzhou, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaNational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaDepartment of Genetics, Yale University School of MedicineNew Haven, CT, USANational Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of SciencesBeijing, ChinaKey Laboratory of Medical Neurobiology of the Ministry of Health of China, Department of Neurobiology, Institute of Neuroscience, Zhejiang University School of MedicineHangzhou, ChinaSynaptic vesicles (SV) store various neurotransmitters that are released at the synapse. The molecular mechanisms of biogenesis, exocytosis, and endocytosis for SV, however, remain largely elusive. In this study, using Complex Object Parametric Analysis and Sorter (COPAS) to monitor the fluorescence of synapto-pHluorin (SpH), we performed a whole-genome RNAi screen in C. elegans to identify novel genetic modulators in SV cycling. One hundred seventy six genes that up-regulating SpH fluorescence and 96 genes that down-regulating SpH fluorescence were identified after multi-round screen. Among these genes, B0035.1 (bugz-1) encodes ortholog of mammalian C2H2 zinc-finger protein BuGZ/ZNF207, which is a spindle assembly checkpoint protein essential for mitosis in human cells. Combining electrophysiology, imaging and behavioral assays, we reveal that depletion of BuGZ-1 results in defects in locomotion. We further demonstrate that BuGZ-1 promotes SV recycling by regulating the expression levels of endocytosis-related genes such as rab11.1. Therefore, we have identified a bunch of potential genetic modulators in SV cycling, and revealed an unexpected role of BuGZ-1 in regulating synaptic transmission.http://journal.frontiersin.org/article/10.3389/fnmol.2017.00141/fullRNAi screensynaptic transmissionC. elegansC2H2 zinc-finger proteinsynaptic vesicles |
| spellingShingle | Mei Han Mei Han Mei Han Wenjuan Zou Hao Chang Hao Chang Yong Yu Haining Zhang Shitian Li Hankui Cheng Guifeng Wei Yan Chen Valerie Reinke Tao Xu Lijun Kang A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans Frontiers in Molecular Neuroscience RNAi screen synaptic transmission C. elegans C2H2 zinc-finger protein synaptic vesicles |
| title | A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans |
| title_full | A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans |
| title_fullStr | A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans |
| title_full_unstemmed | A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans |
| title_short | A Systematic RNAi Screen Reveals a Novel Role of a Spindle Assembly Checkpoint Protein BuGZ in Synaptic Transmission in C. elegans |
| title_sort | systematic rnai screen reveals a novel role of a spindle assembly checkpoint protein bugz in synaptic transmission in c elegans |
| topic | RNAi screen synaptic transmission C. elegans C2H2 zinc-finger protein synaptic vesicles |
| url | http://journal.frontiersin.org/article/10.3389/fnmol.2017.00141/full |
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