Fusion pore in exocytosis: more than an exit gate? A β-cell perspective
Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifus...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2017
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| _version_ | 1797064192541327360 |
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| author | Hastoy, B Clark, A Rorsman, P Lang, J |
| author_facet | Hastoy, B Clark, A Rorsman, P Lang, J |
| author_sort | Hastoy, B |
| collection | OXFORD |
| description | Secretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo. We consider some of the still open questions such as the nature of the initiation of the fusion pore, the structure and the role of the Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor (SNARE) transmembrane domains and their influence on the dynamics and regulation of exocytosis. We discuss how the membrane composition and protein-lipid interactions influence the likelihood of the nascent fusion pore forming. We relate these factors to the hypothesis that fusion pore expansion could be affected in type-2 diabetes via changes in disease-related gene transcription and alterations in the circulating lipid profile. Detailed characterisation of the dynamics of the fusion pore in vitro will contribute to understanding the larger issue of insulin secretory defects in diabetes. |
| first_indexed | 2024-03-06T21:10:44Z |
| format | Journal article |
| id | oxford-uuid:3e10edf0-b038-45e2-bb4d-4d61141c0c6b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T21:10:44Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:3e10edf0-b038-45e2-bb4d-4d61141c0c6b2022-03-26T14:23:12ZFusion pore in exocytosis: more than an exit gate? A β-cell perspectiveJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:3e10edf0-b038-45e2-bb4d-4d61141c0c6bEnglishSymplectic Elements at OxfordElsevier2017Hastoy, BClark, ARorsman, PLang, JSecretory vesicle exocytosis is a fundamental biological event and the process by which hormones (like insulin) are released into the blood. Considerable progress has been made in understanding this precisely orchestrated sequence of events from secretory vesicle docked at the cell membrane, hemifusion, to the opening of a membrane fusion pore. The exact biophysical and physiological regulation of these events implies a close interaction between membrane proteins and lipids in a confined space and constrained geometry to ensure appropriate delivery of cargo. We consider some of the still open questions such as the nature of the initiation of the fusion pore, the structure and the role of the Soluble N-ethylmaleimide-sensitive-factor Attachment protein REceptor (SNARE) transmembrane domains and their influence on the dynamics and regulation of exocytosis. We discuss how the membrane composition and protein-lipid interactions influence the likelihood of the nascent fusion pore forming. We relate these factors to the hypothesis that fusion pore expansion could be affected in type-2 diabetes via changes in disease-related gene transcription and alterations in the circulating lipid profile. Detailed characterisation of the dynamics of the fusion pore in vitro will contribute to understanding the larger issue of insulin secretory defects in diabetes. |
| spellingShingle | Hastoy, B Clark, A Rorsman, P Lang, J Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title | Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title_full | Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title_fullStr | Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title_full_unstemmed | Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title_short | Fusion pore in exocytosis: more than an exit gate? A β-cell perspective |
| title_sort | fusion pore in exocytosis more than an exit gate a β cell perspective |
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