Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent

Cary R Boyd-Shiwarski; Daniel J Shiwarski; Ankita Roy; Hima N Namboodiri; Lubika J Nkashama; Jian Xie; Kara L McClain; Allison Marciszyn; Thomas R Kleyman; Roderick J Tan; Donna B Stolz; Manojkumar A Puthenveedu; Chou-Long Huang; Arohan R Subramanya

doi:10.1091/mbc.E17-08-0529

Back

Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent

Journal article

Open access

Peer reviewed

Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent

Cary R Boyd-Shiwarski, Daniel J Shiwarski, Ankita Roy, Hima N Namboodiri, Lubika J Nkashama, Jian Xie, Kara L McClain, Allison Marciszyn, Thomas R Kleyman, Roderick J Tan, …

Molecular biology of the cell, Vol.29(4), pp.499-509

02/15/2018

DOI: 10.1091/mbc.E17-08-0529

PMCID: PMC6014176

PMID: 29237822

Files and links (1)

url

https://doi.org/10.1091/mbc.E17-08-0529View

Published (Version of record) Open Access

Abstract

With-no-lysine (WNK) kinases coordinate volume and potassium homeostasis by regulating renal tubular electrolyte transport. In the distal convoluted tubule (DCT), potassium imbalance causes WNK signaling complexes to concentrate into large discrete foci, which we call "WNK bodies." Although these structures have been reported previously, the mechanisms that drive their assembly remain obscure. Here, we show that kidney-specific WNK1 (KS-WNK1), a truncated kinase-defective WNK1 isoform that is highly expressed in the DCT, is critical for WNK body formation. While morphologically distinct WNK bodies were evident in the distal tubules of mice subjected to dietary potassium loading and restriction, KS-WNK1 knockout mice were deficient in these structures under identical conditions. Combining in vivo observations in kidney with reconstitution studies in cell culture, we found that WNK bodies are dynamic membraneless foci that are distinct from conventional organelles, colocalize with the ribosomal protein L22, and cluster the WNK signaling pathway. The formation of WNK bodies requires an evolutionarily conserved cysteine-rich hydrophobic motif harbored within a unique N-terminal exon of KS-WNK1. We propose that WNK bodies are not pathological aggregates, but rather are KS-WNK1-dependent microdomains of the DCT cytosol that modulate WNK signaling during physiological shifts in potassium balance.

Potassium - metabolism

WNK Lysine-Deficient Protein Kinase 1 - metabolism

Signal Transduction

Exons

Humans

Mice, Inbred C57BL

Mice, 129 Strain

Potassium - pharmacology

Microscopy, Immunoelectron

Mice, Knockout

Kidney - metabolism

Animals

HEK293 Cells

Hydrophobic and Hydrophilic Interactions

Mice

WNK Lysine-Deficient Protein Kinase 1 - genetics

Details

Title: Subtitle: Potassium-regulated distal tubule WNK bodies are kidney-specific WNK1 dependent
Creators: Cary R Boyd-Shiwarski - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Daniel J Shiwarski - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213
Ankita Roy - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Hima N Namboodiri - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Lubika J Nkashama - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Jian Xie - Department of Internal Medicine, Division of Nephrology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Kara L McClain - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Allison Marciszyn - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Thomas R Kleyman - Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Roderick J Tan - Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Donna B Stolz - Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261
Manojkumar A Puthenveedu - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA 15213
Chou-Long Huang - Department of Internal Medicine, Division of Nephrology, University of Iowa Carver College of Medicine, Iowa City, IA 52242
Arohan R Subramanya - VA Pittsburgh Healthcare System, Pittsburgh, PA 15240
Resource Type: Journal article
Publication Details: Molecular biology of the cell, Vol.29(4), pp.499-509
DOI: 10.1091/mbc.E17-08-0529
PMID: 29237822
PMCID: PMC6014176
NLM abbreviation: Mol Biol Cell
ISSN: 1059-1524
eISSN: 1939-4586
Grant note: P30 DK079307 / NIDDK NIH HHS R01 DK111542 / NIDDK NIH HHS R01 DK098145 / NIDDK NIH HHS R01 DK038470 / NIDDK NIH HHS T35 DK065521 / NIDDK NIH HHS R01 GM117425 / NIGMS NIH HHS T32 DK061296 / NIDDK NIH HHS
Language: English
Date published: 02/15/2018
Academic Unit: Nephrology; Internal Medicine
Record Identifier: 9984094579002771

Metrics

138 Record Views

67 Times Cited - Web of Science