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Structural Insights into AQP2 Targeting to Multivesicular Bodies
Vasopressin-dependent trafficking of AQP2 in the renal collecting duct is crucial for the regulation of water homeostasis. This process involves the targeting of AQP2 to the apical membrane during dehydration as well as its removal when hydration levels have been restored. The latter involves AQP2 e...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862464/ https://www.ncbi.nlm.nih.gov/pubmed/31661793 http://dx.doi.org/10.3390/ijms20215351 |
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author | Roche, Jennifer Virginia Nesverova, Veronika Olsson, Caroline Deen, Peter MT Törnroth-Horsefield, Susanna |
author_facet | Roche, Jennifer Virginia Nesverova, Veronika Olsson, Caroline Deen, Peter MT Törnroth-Horsefield, Susanna |
author_sort | Roche, Jennifer Virginia |
collection | PubMed |
description | Vasopressin-dependent trafficking of AQP2 in the renal collecting duct is crucial for the regulation of water homeostasis. This process involves the targeting of AQP2 to the apical membrane during dehydration as well as its removal when hydration levels have been restored. The latter involves AQP2 endocytosis and sorting into multivesicular bodies (MVB), from where it may be recycled, degraded in lysosomes, or released into urine via exosomes. The lysosomal trafficking regulator-interacting protein 5 (LIP5) plays a crucial role in this by coordinating the actions of the endosomal sorting complex required for transport III (ESCRT-III) and vacuolar protein sorting 4 (Vps4) ATPase, resulting in the insertion of AQP2 into MVB inner vesicles. While the interaction between LIP5 and the ESCRT-III complex and Vps4 is well characterized, very little is known about how LIP5 interacts with AQP2 or any other membrane protein cargo. Here, we use a combination of fluorescence spectroscopy and computer modeling to provide a structural model of how LIP5 interacts with human AQP2. We demonstrate that, the AQP2 tetramer binds up to two LIP5 molecules and that the interaction is similar to that seen in the complex between LIP5 and the ESCRT-III component, charged multivesicular body protein 1B (CHMP1B). These studies give the very first structural insights into how LIP5 enables membrane protein insertion into MVB inner vesicles and significantly increase our understanding of the AQP2 trafficking mechanism. |
format | Online Article Text |
id | pubmed-6862464 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-68624642019-12-05 Structural Insights into AQP2 Targeting to Multivesicular Bodies Roche, Jennifer Virginia Nesverova, Veronika Olsson, Caroline Deen, Peter MT Törnroth-Horsefield, Susanna Int J Mol Sci Article Vasopressin-dependent trafficking of AQP2 in the renal collecting duct is crucial for the regulation of water homeostasis. This process involves the targeting of AQP2 to the apical membrane during dehydration as well as its removal when hydration levels have been restored. The latter involves AQP2 endocytosis and sorting into multivesicular bodies (MVB), from where it may be recycled, degraded in lysosomes, or released into urine via exosomes. The lysosomal trafficking regulator-interacting protein 5 (LIP5) plays a crucial role in this by coordinating the actions of the endosomal sorting complex required for transport III (ESCRT-III) and vacuolar protein sorting 4 (Vps4) ATPase, resulting in the insertion of AQP2 into MVB inner vesicles. While the interaction between LIP5 and the ESCRT-III complex and Vps4 is well characterized, very little is known about how LIP5 interacts with AQP2 or any other membrane protein cargo. Here, we use a combination of fluorescence spectroscopy and computer modeling to provide a structural model of how LIP5 interacts with human AQP2. We demonstrate that, the AQP2 tetramer binds up to two LIP5 molecules and that the interaction is similar to that seen in the complex between LIP5 and the ESCRT-III component, charged multivesicular body protein 1B (CHMP1B). These studies give the very first structural insights into how LIP5 enables membrane protein insertion into MVB inner vesicles and significantly increase our understanding of the AQP2 trafficking mechanism. MDPI 2019-10-28 /pmc/articles/PMC6862464/ /pubmed/31661793 http://dx.doi.org/10.3390/ijms20215351 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Roche, Jennifer Virginia Nesverova, Veronika Olsson, Caroline Deen, Peter MT Törnroth-Horsefield, Susanna Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title | Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title_full | Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title_fullStr | Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title_full_unstemmed | Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title_short | Structural Insights into AQP2 Targeting to Multivesicular Bodies |
title_sort | structural insights into aqp2 targeting to multivesicular bodies |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862464/ https://www.ncbi.nlm.nih.gov/pubmed/31661793 http://dx.doi.org/10.3390/ijms20215351 |
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