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The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission

Classical dynamins bind the plasma membrane–localized phosphatidylinositol-4,5-bisphosphate using the pleckstrin-homology domain (PHD) and engage in rapid membrane fission during synaptic vesicle recycling. This domain is conspicuously absent among extant bacterial and mitochondrial dynamins, howeve...

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Detalles Bibliográficos
Autores principales: Dar, Srishti, Pucadyil, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221619/
https://www.ncbi.nlm.nih.gov/pubmed/28035046
http://dx.doi.org/10.1091/mbc.E16-09-0640
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author Dar, Srishti
Pucadyil, Thomas J.
author_facet Dar, Srishti
Pucadyil, Thomas J.
author_sort Dar, Srishti
collection PubMed
description Classical dynamins bind the plasma membrane–localized phosphatidylinositol-4,5-bisphosphate using the pleckstrin-homology domain (PHD) and engage in rapid membrane fission during synaptic vesicle recycling. This domain is conspicuously absent among extant bacterial and mitochondrial dynamins, however, where loop regions manage membrane recruitment. Inspired by the core design of bacterial and mitochondrial dynamins, we reengineered the classical dynamin by replacing its PHD with a polyhistidine or polylysine linker. Remarkably, when recruited via chelator or anionic lipids, respectively, the reengineered dynamin displayed the capacity to constrict and sever membrane tubes. However, when analyzed at single-event resolution, the tube-severing process displayed long-lived, highly constricted prefission intermediates that contributed to 10-fold reduction in bulk rates of membrane fission. Our results indicate that the PHD acts as a catalyst in dynamin-induced membrane fission and rationalize its adoption to meet the physiologic requirement of a fast-acting membrane fission apparatus.
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spelling pubmed-52216192017-03-16 The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission Dar, Srishti Pucadyil, Thomas J. Mol Biol Cell Articles Classical dynamins bind the plasma membrane–localized phosphatidylinositol-4,5-bisphosphate using the pleckstrin-homology domain (PHD) and engage in rapid membrane fission during synaptic vesicle recycling. This domain is conspicuously absent among extant bacterial and mitochondrial dynamins, however, where loop regions manage membrane recruitment. Inspired by the core design of bacterial and mitochondrial dynamins, we reengineered the classical dynamin by replacing its PHD with a polyhistidine or polylysine linker. Remarkably, when recruited via chelator or anionic lipids, respectively, the reengineered dynamin displayed the capacity to constrict and sever membrane tubes. However, when analyzed at single-event resolution, the tube-severing process displayed long-lived, highly constricted prefission intermediates that contributed to 10-fold reduction in bulk rates of membrane fission. Our results indicate that the PHD acts as a catalyst in dynamin-induced membrane fission and rationalize its adoption to meet the physiologic requirement of a fast-acting membrane fission apparatus. The American Society for Cell Biology 2017-01-01 /pmc/articles/PMC5221619/ /pubmed/28035046 http://dx.doi.org/10.1091/mbc.E16-09-0640 Text en © 2017 Dar and Pucadyil. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Dar, Srishti
Pucadyil, Thomas J.
The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title_full The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title_fullStr The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title_full_unstemmed The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title_short The pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
title_sort pleckstrin-homology domain of dynamin is dispensable for membrane constriction and fission
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5221619/
https://www.ncbi.nlm.nih.gov/pubmed/28035046
http://dx.doi.org/10.1091/mbc.E16-09-0640
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