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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...

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Autores principales: Roche, Jennifer Virginia, Nesverova, Veronika, Olsson, Caroline, Deen, Peter MT, Törnroth-Horsefield, Susanna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
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.
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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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