A mechanism for exocytotic arrest by the Complexin C-terminus
ComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2018-07-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/38981 |
| _version_ | 1811253276998369280 |
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| author | Mazen Makke Maria Mantero Martinez Surya Gaya Yvonne Schwarz Walentina Frisch Lina Silva-Bermudez Martin Jung Ralf Mohrmann Madhurima Dhara Dieter Bruns |
| author_facet | Mazen Makke Maria Mantero Martinez Surya Gaya Yvonne Schwarz Walentina Frisch Lina Silva-Bermudez Martin Jung Ralf Mohrmann Madhurima Dhara Dieter Bruns |
| author_sort | Mazen Makke |
| collection | DOAJ |
| description | ComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into mouse chromaffin cells enhances synchronous release by diminishing premature vesicle fusion like full-length CpxII, indicating a direct, inhibitory function of the CTD that sets the magnitude of the primed vesicle pool. We describe a high degree of structural similarity between the CpxII CTD and the SNAP25-SN1 domain (C-terminal half) and show that the CTD peptide lowers the rate of SDS-resistant SNARE complex formation in vitro. Moreover, corresponding CpxII:SNAP25 chimeras do restore complexin’s function and even ‘superclamp’ tonic secretion. Collectively, these results support a so far unrecognized clamping mechanism wherein the CpxII C-terminus hinders spontaneous SNARE complex assembly, enabling the build-up of a release-ready pool of vesicles for synchronized Ca2+-triggered exocytosis. |
| first_indexed | 2024-04-12T16:47:30Z |
| format | Article |
| id | doaj.art-dec18f4c9db8408180aac8635f335433 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:47:30Z |
| publishDate | 2018-07-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-dec18f4c9db8408180aac8635f3354332022-12-22T03:24:31ZengeLife Sciences Publications LtdeLife2050-084X2018-07-01710.7554/eLife.38981A mechanism for exocytotic arrest by the Complexin C-terminusMazen Makke0Maria Mantero Martinez1Surya Gaya2https://orcid.org/0000-0003-0163-5748Yvonne Schwarz3Walentina Frisch4Lina Silva-Bermudez5Martin Jung6https://orcid.org/0000-0002-1482-7020Ralf Mohrmann7Madhurima Dhara8https://orcid.org/0000-0001-7745-472XDieter Bruns9https://orcid.org/0000-0002-2497-1878Institute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Medical Biochemistry and Molecular Biology, University of Saarland, Homburg, GermanyInstitute for Physiology, Otto-von-Guericke University, Magdeburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyInstitute for Physiology, Center of Integrative Physiology and Molecular Medicine, University of Saarland, Homburg, GermanyComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into mouse chromaffin cells enhances synchronous release by diminishing premature vesicle fusion like full-length CpxII, indicating a direct, inhibitory function of the CTD that sets the magnitude of the primed vesicle pool. We describe a high degree of structural similarity between the CpxII CTD and the SNAP25-SN1 domain (C-terminal half) and show that the CTD peptide lowers the rate of SDS-resistant SNARE complex formation in vitro. Moreover, corresponding CpxII:SNAP25 chimeras do restore complexin’s function and even ‘superclamp’ tonic secretion. Collectively, these results support a so far unrecognized clamping mechanism wherein the CpxII C-terminus hinders spontaneous SNARE complex assembly, enabling the build-up of a release-ready pool of vesicles for synchronized Ca2+-triggered exocytosis.https://elifesciences.org/articles/38981vesicle fusionneurotransmitter releaseexocytotic arrestcomplexinSNAREs |
| spellingShingle | Mazen Makke Maria Mantero Martinez Surya Gaya Yvonne Schwarz Walentina Frisch Lina Silva-Bermudez Martin Jung Ralf Mohrmann Madhurima Dhara Dieter Bruns A mechanism for exocytotic arrest by the Complexin C-terminus eLife vesicle fusion neurotransmitter release exocytotic arrest complexin SNAREs |
| title | A mechanism for exocytotic arrest by the Complexin C-terminus |
| title_full | A mechanism for exocytotic arrest by the Complexin C-terminus |
| title_fullStr | A mechanism for exocytotic arrest by the Complexin C-terminus |
| title_full_unstemmed | A mechanism for exocytotic arrest by the Complexin C-terminus |
| title_short | A mechanism for exocytotic arrest by the Complexin C-terminus |
| title_sort | mechanism for exocytotic arrest by the complexin c terminus |
| topic | vesicle fusion neurotransmitter release exocytotic arrest complexin SNAREs |
| url | https://elifesciences.org/articles/38981 |
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