The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels
Presynaptic calcium channel function is critical for converting electrical information into chemical communication but the molecules in the active zone that sculpt this function are poorly understood. We show that Munc13, an active-zone protein essential for exocytosis, also controls presynaptic vol...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2015-07-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/07728 |
| _version_ | 1818019104777306112 |
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| author | Nathaniel Calloway Géraldine Gouzer Mingyu Xue Timothy A Ryan |
| author_facet | Nathaniel Calloway Géraldine Gouzer Mingyu Xue Timothy A Ryan |
| author_sort | Nathaniel Calloway |
| collection | DOAJ |
| description | Presynaptic calcium channel function is critical for converting electrical information into chemical communication but the molecules in the active zone that sculpt this function are poorly understood. We show that Munc13, an active-zone protein essential for exocytosis, also controls presynaptic voltage-gated calcium channel (VGCC) function dictating their behavior during various forms of activity. We demonstrate that in vitro Munc13 interacts with voltage-VGCCs via a pair of basic residues in Munc13's C2B domain. We show that elimination of this interaction by either removal of Munc13 or replacement of Munc13 with a Munc13 C2B mutant alters synaptic VGCC's response to and recovery from high-frequency action potential bursts and alters calcium influx from single action potential stimuli. These studies illustrate a novel form of synaptic modulation and show that Munc13 is poised to profoundly impact information transfer at nerve terminals by controlling both vesicle priming and the trigger for exocytosis. |
| first_indexed | 2024-04-14T07:47:53Z |
| format | Article |
| id | doaj.art-62ab794161014ccb98c2f5ae840ee848 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:47:53Z |
| publishDate | 2015-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-62ab794161014ccb98c2f5ae840ee8482022-12-22T02:05:17ZengeLife Sciences Publications LtdeLife2050-084X2015-07-01410.7554/eLife.07728The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channelsNathaniel Calloway0Géraldine Gouzer1Mingyu Xue2Timothy A Ryan3Department of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesDepartment of Biochemistry, Weill Cornell Medical College, New York, United StatesPresynaptic calcium channel function is critical for converting electrical information into chemical communication but the molecules in the active zone that sculpt this function are poorly understood. We show that Munc13, an active-zone protein essential for exocytosis, also controls presynaptic voltage-gated calcium channel (VGCC) function dictating their behavior during various forms of activity. We demonstrate that in vitro Munc13 interacts with voltage-VGCCs via a pair of basic residues in Munc13's C2B domain. We show that elimination of this interaction by either removal of Munc13 or replacement of Munc13 with a Munc13 C2B mutant alters synaptic VGCC's response to and recovery from high-frequency action potential bursts and alters calcium influx from single action potential stimuli. These studies illustrate a novel form of synaptic modulation and show that Munc13 is poised to profoundly impact information transfer at nerve terminals by controlling both vesicle priming and the trigger for exocytosis.https://elifesciences.org/articles/07728Munc13calcium channelplasticity |
| spellingShingle | Nathaniel Calloway Géraldine Gouzer Mingyu Xue Timothy A Ryan The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels eLife Munc13 calcium channel plasticity |
| title | The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels |
| title_full | The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels |
| title_fullStr | The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels |
| title_full_unstemmed | The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels |
| title_short | The active-zone protein Munc13 controls the use-dependence of presynaptic voltage-gated calcium channels |
| title_sort | active zone protein munc13 controls the use dependence of presynaptic voltage gated calcium channels |
| topic | Munc13 calcium channel plasticity |
| url | https://elifesciences.org/articles/07728 |
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