Moustaq, L., Smaczynska-de Rooij, I.I., Palmer, S.E. et al. (2 more authors) (2016) Insights into dynamin-associated disorders through analysis of equivalent mutations in the yeast dynamin Vps1. Microbial Cell, 3 (4). pp. 147-158.
Abstract
The dynamins represent a superfamily of proteins that have been shown to function in a wide range of membrane fusion and fission events. An increasing number of mutations in the human classical dynamins, Dyn-1 and Dyn-2 has been reported, with diseases caused by these changes ranging from Charcot-Marie-Tooth disorder to epileptic encephalopathies. The budding yeast, Saccharomyces cerevisiae expresses a single dynamin-related protein that functions in membrane trafficking, and is considered to play a similar role to Dyn-1 and Dyn-2 during scission of endocytic vesicles at the plasma membrane. Large parts of the dynamin protein are highly conserved across species and this has enabled us in this study to select a number of disease causing mutations and to generate equivalent mutations in Vps1. We have then studied these mutants using both cellular and biochemical assays to ascertain functions of the protein that have been affected by the changes. Specifically, we demonstrate that the Vps1-G397R mutation (Dyn-2 G358R) disrupts protein oligomerization, Vps1-A447T (Dyn-1 A408T) affects the scission stage of endocytosis, while Vps1-R298L (Dyn-1 R256L) affects lipid binding specificity and possibly an early stage in endocytosis. Overall, we consider that the yeast model will potentially provide an avenue for rapid analysis of new dynamin mutations in order to understand the underlying mechanisms that they disrupt.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2016 Moustaq et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/), which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged. |
Keywords: | Dynamin; Charcot-Marie-Tooth; Epilepsy; Disease mutation; Saccharomyces cerevisiae |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Science (Sheffield) > School of Biosciences (Sheffield) > Department of Biomedical Science (Sheffield) |
Funding Information: | Funder Grant number BIOTECHNOLOGY AND BIOLOGICAL SCIENCES RESEARCH COUNCIL (BBSRC) BB/K002511/1 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 15 Jul 2016 15:07 |
Last Modified: | 15 Jul 2016 15:07 |
Published Version: | http://dx.doi.org/10.15698/mic2016.04.490 |
Status: | Published |
Publisher: | Shared Science Publishers |
Refereed: | Yes |
Identification Number: | 10.15698/mic2016.04.490 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:101670 |