CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles
Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docke...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2023-02-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/81407 |
| _version_ | 1797858368641040384 |
|---|---|
| author | Brian D Mueller Sean A Merrill Shigeki Watanabe Ping Liu Longgang Niu Anish Singh Pablo Maldonado-Catala Alex Cherry Matthew S Rich Malan Silva Andres Villu Maricq Zhao-Wen Wang Erik M Jorgensen |
| author_facet | Brian D Mueller Sean A Merrill Shigeki Watanabe Ping Liu Longgang Niu Anish Singh Pablo Maldonado-Catala Alex Cherry Matthew S Rich Malan Silva Andres Villu Maricq Zhao-Wen Wang Erik M Jorgensen |
| author_sort | Brian D Mueller |
| collection | DOAJ |
| description | Activation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release. |
| first_indexed | 2024-04-09T21:12:19Z |
| format | Article |
| id | doaj.art-aff5d801f72a4f8aba271286f81e70b1 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-09T21:12:19Z |
| publishDate | 2023-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-aff5d801f72a4f8aba271286f81e70b12023-03-28T15:42:18ZengeLife Sciences Publications LtdeLife2050-084X2023-02-011210.7554/eLife.81407CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesiclesBrian D Mueller0https://orcid.org/0000-0002-6525-7101Sean A Merrill1Shigeki Watanabe2https://orcid.org/0000-0001-7580-8141Ping Liu3Longgang Niu4https://orcid.org/0000-0001-7209-7436Anish Singh5Pablo Maldonado-Catala6Alex Cherry7Matthew S Rich8Malan Silva9Andres Villu Maricq10Zhao-Wen Wang11https://orcid.org/0000-0003-3574-8556Erik M Jorgensen12https://orcid.org/0000-0002-2978-8028Howard Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesDepartment of Neuroscience, University of Connecticut Medical School, Farmington, United StatesDepartment of Neuroscience, University of Connecticut Medical School, Farmington, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesDepartment of Neurobiology, University of Utah, Salt Lake City, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesDepartment of Neurobiology, University of Utah, Salt Lake City, United StatesDepartment of Neuroscience, University of Connecticut Medical School, Farmington, United StatesHoward Hughes Medical Institute, School of Biological Sciences, University of Utah, Salt Lake City, United StatesActivation of voltage-gated calcium channels at presynaptic terminals leads to local increases in calcium and the fusion of synaptic vesicles containing neurotransmitter. Presynaptic output is a function of the density of calcium channels, the dynamic properties of the channel, the distance to docked vesicles, and the release probability at the docking site. We demonstrate that at Caenorhabditis elegans neuromuscular junctions two different classes of voltage-gated calcium channels, CaV2 and CaV1, mediate the release of distinct pools of synaptic vesicles. CaV2 channels are concentrated in densely packed clusters ~250 nm in diameter with the active zone proteins Neurexin, α-Liprin, SYDE, ELKS/CAST, RIM-BP, α-Catulin, and MAGI1. CaV2 channels are colocalized with the priming protein UNC-13L and mediate the fusion of vesicles docked within 33 nm of the dense projection. CaV2 activity is amplified by ryanodine receptor release of calcium from internal stores, triggering fusion up to 165 nm from the dense projection. By contrast, CaV1 channels are dispersed in the synaptic varicosity, and are colocalized with UNC-13S. CaV1 and ryanodine receptors are separated by just 40 nm, and vesicle fusion mediated by CaV1 is completely dependent on the ryanodine receptor. Distinct synaptic vesicle pools, released by different calcium channels, could be used to tune the speed, voltage-dependence, and quantal content of neurotransmitter release.https://elifesciences.org/articles/81407L-typeN-typesuper-resolution microscopyMunc13calcium channelsryanodine receptor |
| spellingShingle | Brian D Mueller Sean A Merrill Shigeki Watanabe Ping Liu Longgang Niu Anish Singh Pablo Maldonado-Catala Alex Cherry Matthew S Rich Malan Silva Andres Villu Maricq Zhao-Wen Wang Erik M Jorgensen CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles eLife L-type N-type super-resolution microscopy Munc13 calcium channels ryanodine receptor |
| title | CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| title_full | CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| title_fullStr | CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| title_full_unstemmed | CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| title_short | CaV1 and CaV2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| title_sort | cav1 and cav2 calcium channels mediate the release of distinct pools of synaptic vesicles |
| topic | L-type N-type super-resolution microscopy Munc13 calcium channels ryanodine receptor |
| url | https://elifesciences.org/articles/81407 |
| work_keys_str_mv | AT briandmueller cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT seanamerrill cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT shigekiwatanabe cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT pingliu cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT longgangniu cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT anishsingh cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT pablomaldonadocatala cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT alexcherry cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT matthewsrich cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT malansilva cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT andresvillumaricq cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT zhaowenwang cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles AT erikmjorgensen cav1andcav2calciumchannelsmediatethereleaseofdistinctpoolsofsynapticvesicles |