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Structural insights into AQP2 targeting to multivesicular bodies

Roche, Jennifer Virginia LU ; Nesverova, Veronika LU ; Olsson, Caroline ; Deen, Peter M.T. and Törnroth-Horsefield, Susanna LU (2019) In International Journal of Molecular Sciences 20(21).
Abstract

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... (More)

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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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Aquaporin 2, Lysosomal trafficking regulator-interacting protein 5, Multivesicular bodies, Protein sorting, Trafficking, Water channel
in
International Journal of Molecular Sciences
volume
20
issue
21
article number
5351
publisher
MDPI AG
external identifiers
  • pmid:31661793
  • scopus:85074283666
ISSN
1661-6596
DOI
10.3390/ijms20215351
language
English
LU publication?
yes
id
eb800471-1ec7-4570-a7af-0da6213d7634
date added to LUP
2019-11-15 14:30:51
date last changed
2024-10-02 16:28:12
@article{eb800471-1ec7-4570-a7af-0da6213d7634,
  abstract     = {{<p>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.</p>}},
  author       = {{Roche, Jennifer Virginia and Nesverova, Veronika and Olsson, Caroline and Deen, Peter M.T. and Törnroth-Horsefield, Susanna}},
  issn         = {{1661-6596}},
  keywords     = {{Aquaporin 2; Lysosomal trafficking regulator-interacting protein 5; Multivesicular bodies; Protein sorting; Trafficking; Water channel}},
  language     = {{eng}},
  month        = {{11}},
  number       = {{21}},
  publisher    = {{MDPI AG}},
  series       = {{International Journal of Molecular Sciences}},
  title        = {{Structural insights into AQP2 targeting to multivesicular bodies}},
  url          = {{http://dx.doi.org/10.3390/ijms20215351}},
  doi          = {{10.3390/ijms20215351}},
  volume       = {{20}},
  year         = {{2019}},
}