Cargando…
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...
Autores principales: | , |
---|---|
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 |
_version_ | 1782492852053344256 |
---|---|
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. |
format | Online Article Text |
id | pubmed-5221619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT darsrishti thepleckstrinhomologydomainofdynaminisdispensableformembraneconstrictionandfission AT pucadyilthomasj thepleckstrinhomologydomainofdynaminisdispensableformembraneconstrictionandfission AT darsrishti pleckstrinhomologydomainofdynaminisdispensableformembraneconstrictionandfission AT pucadyilthomasj pleckstrinhomologydomainofdynaminisdispensableformembraneconstrictionandfission |