Header

UZH-Logo

Maintenance Infos

Rab-GAP TBC1D4 (AS160) is dispensable for the renal control of sodium and water homeostasis but regulates GLUT4 in mouse kidney


Di Chiara, Marianna; Glaudemans, Bob; Loffing-Cueni, Dominique; Odermatt, Alex; Al-Hasani, Hadi; Devuyst, Olivier; Faresse, Nourdine; Loffing, Johannes (2015). Rab-GAP TBC1D4 (AS160) is dispensable for the renal control of sodium and water homeostasis but regulates GLUT4 in mouse kidney. American Journal of Physiology. Renal, Fluid and Electrolyte Physiology, 309(9):F779-F790.

Abstract

The Rab GTPase-activating protein TBC1D4 (AS160) controls trafficking of the glucose transporter GLUT4 in adipocytes and skeletal muscle cells. TBC1D4 is also highly abundant in the renal distal tubule, although its role in this tubule is so far unknown. In vitro studies suggest that it is involved in the regulation of renal transporters and channels such as the epithelial sodium channel (ENaC), aquaporin-2 (AQP2), and the Na(+)-K(+)-ATPase. To assess the physiological role of TBC1D4 in the kidney, wild-type (TBC1D4(+/+)) and TBC1D4-deficient (TBC1D4(-/-)) mice were studied. Unexpectedly, neither under standard nor under challenging conditions (low Na(+)/high K(+), water restriction) did TBC1D4(-/-) mice show any difference in urinary Na(+) and K(+) excretion, urine osmolarity, plasma ion and aldosterone levels, and blood pressure compared with TBC1D4(+/+) mice. Also, immunoblotting did not reveal any change in the abundance of major renal sodium- and water-transporting proteins [Na-K-2Cl cotransporter (NKCC2) NKCC2, NaCl cotransporter (NCC), ENaC, AQP2, and the Na(+)-K(+)-ATPase]. However, the abundance of GLUT4, which colocalizes with TBC1D4 along the distal nephron of TBC1D4(+/+) mice, was lower in whole kidney lysates of TBC1D4(-/-) mice than in TBC1D4(+/+) mice. Likewise, primary thick ascending limb (TAL) cells isolated from TBC1D4(-/-) mice showed an increased basal glucose uptake and an abrogated insulin response compared with TAL cells from TBC1D4(+/+) mice. Thus, TBC1D4 is dispensable for the regulation of renal Na(+) and water transport, but may play a role for GLUT4-mediated basolateral glucose uptake in distal tubules. The latter may contribute to the known anaerobic glycolytic capacity of distal tubules during renal ischemia.

Abstract

The Rab GTPase-activating protein TBC1D4 (AS160) controls trafficking of the glucose transporter GLUT4 in adipocytes and skeletal muscle cells. TBC1D4 is also highly abundant in the renal distal tubule, although its role in this tubule is so far unknown. In vitro studies suggest that it is involved in the regulation of renal transporters and channels such as the epithelial sodium channel (ENaC), aquaporin-2 (AQP2), and the Na(+)-K(+)-ATPase. To assess the physiological role of TBC1D4 in the kidney, wild-type (TBC1D4(+/+)) and TBC1D4-deficient (TBC1D4(-/-)) mice were studied. Unexpectedly, neither under standard nor under challenging conditions (low Na(+)/high K(+), water restriction) did TBC1D4(-/-) mice show any difference in urinary Na(+) and K(+) excretion, urine osmolarity, plasma ion and aldosterone levels, and blood pressure compared with TBC1D4(+/+) mice. Also, immunoblotting did not reveal any change in the abundance of major renal sodium- and water-transporting proteins [Na-K-2Cl cotransporter (NKCC2) NKCC2, NaCl cotransporter (NCC), ENaC, AQP2, and the Na(+)-K(+)-ATPase]. However, the abundance of GLUT4, which colocalizes with TBC1D4 along the distal nephron of TBC1D4(+/+) mice, was lower in whole kidney lysates of TBC1D4(-/-) mice than in TBC1D4(+/+) mice. Likewise, primary thick ascending limb (TAL) cells isolated from TBC1D4(-/-) mice showed an increased basal glucose uptake and an abrogated insulin response compared with TAL cells from TBC1D4(+/+) mice. Thus, TBC1D4 is dispensable for the regulation of renal Na(+) and water transport, but may play a role for GLUT4-mediated basolateral glucose uptake in distal tubules. The latter may contribute to the known anaerobic glycolytic capacity of distal tubules during renal ischemia.

Statistics

Citations

1 citation in Web of Science®
1 citation in Scopus®
Google Scholar™

Altmetrics

Additional indexing

Item Type:Journal Article, not refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Anatomy
04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > Center for Integrative Human Physiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:1 November 2015
Deposited On:14 Dec 2015 14:21
Last Modified:05 Apr 2016 19:37
Publisher:American Physiological Society
ISSN:1522-1466
Additional Information:All journals are free accessible after 12 months via HighWire Press
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1152/ajprenal.00139.2015
PubMed ID:26336159

Download

Full text not available from this repository.
View at publisher

Article Networks

TrendTerms

TrendTerms displays relevant terms of the abstract of this publication and related documents on a map. The terms and their relations were extracted from ZORA using word statistics. Their timelines are taken from ZORA as well. The bubble size of a term is proportional to the number of documents where the term occurs. Red, orange, yellow and green colors are used for terms that occur in the current document; red indicates high interlinkedness of a term with other terms, orange, yellow and green decreasing interlinkedness. Blue is used for terms that have a relation with the terms in this document, but occur in other documents.
You can navigate and zoom the map. Mouse-hovering a term displays its timeline, clicking it yields the associated documents.

Author Collaborations