Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain
Priming of secretory vesicles is a prerequisite for their Ca2+-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. M...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2014-11-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221112471400833X |
| _version_ | 1828472358019530752 |
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| author | Cuc Quynh Nguyen Truong Dennis Nestvogel Olga Ratai Claudia Schirra David R. Stevens Nils Brose JeongSeop Rhee Jens Rettig |
| author_facet | Cuc Quynh Nguyen Truong Dennis Nestvogel Olga Ratai Claudia Schirra David R. Stevens Nils Brose JeongSeop Rhee Jens Rettig |
| author_sort | Cuc Quynh Nguyen Truong |
| collection | DOAJ |
| description | Priming of secretory vesicles is a prerequisite for their Ca2+-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. Munc13s execute their priming function through their MUN domain. Given that the MUN domain of Ca2+-dependent activator protein for secretion (CAPS) also binds syntaxin, it was assumed that CAPSs prime vesicles through the same mechanism as Munc13s. We studied naturally occurring splice variants of CAPS2 in CAPS1/CAPS2-deficient cells and found that CAPS2 primes vesicles independently of its MUN domain. Instead, the pleckstrin homology domain of CAPS2 seemingly is essential for its priming function. Our findings indicate a priming mode for secretory vesicles. This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action. |
| first_indexed | 2024-12-11T05:27:47Z |
| format | Article |
| id | doaj.art-6f5ca7586e3c439d974f8979710446f6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-11T05:27:47Z |
| publishDate | 2014-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-6f5ca7586e3c439d974f8979710446f62022-12-22T01:19:31ZengElsevierCell Reports2211-12472014-11-019390290910.1016/j.celrep.2014.09.050Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN DomainCuc Quynh Nguyen Truong0Dennis Nestvogel1Olga Ratai2Claudia Schirra3David R. Stevens4Nils Brose5JeongSeop Rhee6Jens Rettig7Institute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, GermanyNeurophysiology Group, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, GermanyInstitute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, GermanyInstitute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, GermanyInstitute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, GermanyDepartment of Molecular Neurobiology, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, GermanyNeurophysiology Group, Max-Planck-Institute of Experimental Medicine, 37075 Göttingen, GermanyInstitute of Physiology, Saarland University, Building 59, 66421 Homburg/Saar, GermanyPriming of secretory vesicles is a prerequisite for their Ca2+-dependent fusion with the plasma membrane. The key vesicle priming proteins, Munc13s and CAPSs, are thought to mediate vesicle priming by regulating the conformation of the t-SNARE syntaxin, thereby facilitating SNARE complex assembly. Munc13s execute their priming function through their MUN domain. Given that the MUN domain of Ca2+-dependent activator protein for secretion (CAPS) also binds syntaxin, it was assumed that CAPSs prime vesicles through the same mechanism as Munc13s. We studied naturally occurring splice variants of CAPS2 in CAPS1/CAPS2-deficient cells and found that CAPS2 primes vesicles independently of its MUN domain. Instead, the pleckstrin homology domain of CAPS2 seemingly is essential for its priming function. Our findings indicate a priming mode for secretory vesicles. This process apparently requires membrane phospholipids, does not involve the binding or direct conformational regulation of syntaxin by MUN domains of CAPSs, and is therefore not redundant with Munc13 action.http://www.sciencedirect.com/science/article/pii/S221112471400833X |
| spellingShingle | Cuc Quynh Nguyen Truong Dennis Nestvogel Olga Ratai Claudia Schirra David R. Stevens Nils Brose JeongSeop Rhee Jens Rettig Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain Cell Reports |
| title | Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain |
| title_full | Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain |
| title_fullStr | Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain |
| title_full_unstemmed | Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain |
| title_short | Secretory Vesicle Priming by CAPS Is Independent of Its SNARE-Binding MUN Domain |
| title_sort | secretory vesicle priming by caps is independent of its snare binding mun domain |
| url | http://www.sciencedirect.com/science/article/pii/S221112471400833X |
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