Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics
The presynaptic active zone proteins UNC-13/Munc13s are essential for synaptic vesicle (SV) exocytosis by directly interacting with SV fusion apparatus. An open question is how their association with active zones, hence their position to Ca2+ entry sites, regulates SV release. The N-termini of major...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2013-11-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/01180 |
| _version_ | 1797997563956166656 |
|---|---|
| author | Keming Zhou Tamara M Stawicki Alexandr Goncharov Yishi Jin |
| author_facet | Keming Zhou Tamara M Stawicki Alexandr Goncharov Yishi Jin |
| author_sort | Keming Zhou |
| collection | DOAJ |
| description | The presynaptic active zone proteins UNC-13/Munc13s are essential for synaptic vesicle (SV) exocytosis by directly interacting with SV fusion apparatus. An open question is how their association with active zones, hence their position to Ca2+ entry sites, regulates SV release. The N-termini of major UNC-13/Munc13 isoforms contain a non-calcium binding C2A domain that mediates protein homo- or hetero-meric interactions. Here, we show that the C2A domain of Caenorhabditis elegans UNC-13 regulates release probability of evoked release and its precise active zone localization. Kinetics analysis of SV release supports that the proximity of UNC-13 to Ca2+ entry sites, mediated by the C2A-domain containing N-terminus, is critical for accelerating neurotransmitter release. Additionally, the C2A domain is specifically required for spontaneous release. These data reveal multiple roles of UNC-13 C2A domain, and suggest that spontaneous release and the fast phase of evoked release may involve a common pool of SVs at the active zone. |
| first_indexed | 2024-04-11T10:34:39Z |
| format | Article |
| id | doaj.art-786074d89c894632a8ee4d51c7bbaaed |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:34:39Z |
| publishDate | 2013-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-786074d89c894632a8ee4d51c7bbaaed2022-12-22T04:29:20ZengeLife Sciences Publications LtdeLife2050-084X2013-11-01210.7554/eLife.01180Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kineticsKeming Zhou0Tamara M Stawicki1Alexandr Goncharov2Yishi Jin3Section of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United StatesSection of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Neurosciences Graduate Program, University of California, San Diego, La Jolla, United StatesSection of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United StatesSection of Neurobiology, Division of Biological Sciences, University of California, San Diego, La Jolla, United States; Howard Hughes Medical Institute, University of California, San Diego, La Jolla, United StatesThe presynaptic active zone proteins UNC-13/Munc13s are essential for synaptic vesicle (SV) exocytosis by directly interacting with SV fusion apparatus. An open question is how their association with active zones, hence their position to Ca2+ entry sites, regulates SV release. The N-termini of major UNC-13/Munc13 isoforms contain a non-calcium binding C2A domain that mediates protein homo- or hetero-meric interactions. Here, we show that the C2A domain of Caenorhabditis elegans UNC-13 regulates release probability of evoked release and its precise active zone localization. Kinetics analysis of SV release supports that the proximity of UNC-13 to Ca2+ entry sites, mediated by the C2A-domain containing N-terminus, is critical for accelerating neurotransmitter release. Additionally, the C2A domain is specifically required for spontaneous release. These data reveal multiple roles of UNC-13 C2A domain, and suggest that spontaneous release and the fast phase of evoked release may involve a common pool of SVs at the active zone.https://elifesciences.org/articles/01180UNC-13Munc-13SV release probabilitySV release kineticC2A domainminiSOG |
| spellingShingle | Keming Zhou Tamara M Stawicki Alexandr Goncharov Yishi Jin Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics eLife UNC-13 Munc-13 SV release probability SV release kinetic C2A domain miniSOG |
| title | Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| title_full | Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| title_fullStr | Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| title_full_unstemmed | Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| title_short | Position of UNC-13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| title_sort | position of unc 13 in the active zone regulates synaptic vesicle release probability and release kinetics |
| topic | UNC-13 Munc-13 SV release probability SV release kinetic C2A domain miniSOG |
| url | https://elifesciences.org/articles/01180 |
| work_keys_str_mv | AT kemingzhou positionofunc13intheactivezoneregulatessynapticvesiclereleaseprobabilityandreleasekinetics AT tamaramstawicki positionofunc13intheactivezoneregulatessynapticvesiclereleaseprobabilityandreleasekinetics AT alexandrgoncharov positionofunc13intheactivezoneregulatessynapticvesiclereleaseprobabilityandreleasekinetics AT yishijin positionofunc13intheactivezoneregulatessynapticvesiclereleaseprobabilityandreleasekinetics |