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Reposted by Arohan Subramanya

Journal of Clinical Investigation @jci.org · 08/08/2025

KS-WNK1 augments the effects of dietary potassium intake on renal sodium chloride reabsorption: buff.ly/bmp1w6L Gerardo Gamba & David H. Ellison provide a Commentary on Cary R. Boyd-Shiwarski et al. (buff.ly/Cw7u7c1)

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Reposted by Arohan Subramanya

Cary Boyd-Shiwarski, MD/PhD @caryboyd.bsky.social · 01/08/2025

So exciting to see WNK bodies making the cover of JCI! @pittdeptofmed.bsky.social @arohans.bsky.social @news.upmc.com

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Reposted by Arohan Subramanya

Journal of Clinical Investigation @jci.org · 01/08/2025

A nod and a wink to kidney-specific WNK1 This issue’s cover features work by Cary R. Boyd-Shiwarski et al. on kidney-specific WNK1 as a scaffolding protein that organizes WNK bodies — structures essential for maintaining blood potassium levels: buff.ly/Cw7u7c1

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

Congrats to Cary Boyd-Shiwarski @caryboyd.bsky.social , who expertly saw this through as corresponding author, lab members & alums; and to our collaborators including @simoncwatkins.bsky.social & the Kashlan, Rodan, Huang, and Stocker labs 🎉🥳🍾 /12

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

More generally, this work extends beyond functional studies in cells to support the relevance of biomolecular #condensates in mammalian #physiology, while hinting @ intriguing connections between condensates & public health. 11/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

This is consistent w/ a population-scale metanalysis suggesting that a [K+] <4.0mmol/L is associated w/ increased CV mortality. Perhaps “destressing” the kidney via blood K+ titration could be leveraged to optimize health. Highlighted by Pitt SoM here 10/ www.medschool.pitt.edu/news/kidney-...

medschool.pitt.edu

The Kidney Sounds Its Own Alarm for Dipping Potassium Levels, Pitt Study Finds | School of Medicine | University of Pittsburgh

Photo Caption: An immunofluorescence micrograph of kidney distal convoluted tubules treated with a low potassium diet. The magenta stain is sodium-chloride symporter (NCC), and the green structures ar...

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

In human kidneys, WNK bodies accumulated as [K+] progressively fell below 4.0mmol/L. This suggests that the human DCT hyperactivates 🧂 reabsorption even when K+ is 3.5-4.0. Thus, a K+ in the low-normal range may not be ideal for CV 🫀 health, as it may predispose to salt-sensitive HTN 9/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

Compared to males, K+ restricted female mice were more dependent on WNK bodies for optimal electrolyte balance, indicating that WNK body condensates contribute to nephron sexual dimorphism. 8/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

Using KO and transgenic mouse models, we show that KS-WNK1 activates NCC via WNK bodies during dietary K+ deficiency and inhibits NCC during K+ excess. KS-WNK1 therefore functions as a signal amplifier 📶 that expands the dynamic range of DCT reactivity to [K+] 7/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

…This is because during hypokalemia, the DCT WNK signaling pathway forms specialized condensates termed WNK bodies. These assemblies require KS-WNK1, a truncated DCT-specific WNK1 isoform. KS-WNK1 encodes the large IDR that drives WNK1 phase behavior; basically, it’s a disordered scaffold 6/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

In 2022, we reported that WNKs activate ion transport via IDR-mediated phase separation: www.cell.com/cell/fulltex... . WNK condensates emerged in unicellular species to control cell volume, but we hypothesized that they were repurposed by evolution to regulate kidney tubule ion transport... 5/

cell.com

WNK kinases sense molecular crowding and rescue cell volume via phase separation

WNK1 is a molecular crowding sensor that undergoes cell shrinkage-dependent phase separation to restore cell volume. This study provides a clear link between the intrinsically disordered region-mediat...

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

Some background: The kidney regulates K+ homeostasis. The distal convoluted tubule (DCT) controls Na+ dependent kaliuresis by amplifying small changes in blood K+ into large effects on 🧂 reabsorption via the NaCl cotransporter NCC. WNK kinases mediate this but the details have been unclear 4/

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

The paper was also paired with a lovely editorial penned by two masters of distal nephron physiology, Gerardo Gamba and David Ellison (thank you!) 🙏🏽: 3/ www.jci.org/articles/vie...

jci.org

JCI - KS-WNK1 augments the effects of dietary potassium intake on renal sodium chloride reabsorption

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

This paper integrates years of research that initially started in the kidney, dove into fundamental condensate biology in cells, and circled back to mouse models & a translational analysis in humans. Read the full article here www.jci.org/articles/vie... 2/

jci.org

JCI - Kidney-specific WNK1 amplifies kidney tubule responsiveness to potassium via WNK body condensates

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Arohan Subramanya @arohans.bsky.social · 01/08/2025

Our latest, now in print @jclinical-invest.bsky.social (w/ cover! 🎉) Led by @caryboyd.bsky.social , we identified a functional role for #WNK bodies in K+ homeostasis, highlighting a #condensate 🫧 that can influence kidney physiology & nephron sexual dimorphism, w/ implications for human health 1/

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Reposted by Arohan Subramanya

APS Epithelial Transport Group @aps-etg.bsky.social · 14/04/2025

Hello to all of our friends and colleagues on Bluesky! The epithelial transport group (ETG) is new to the platform, so follow and share to help us grow our network. Don't forget to join us next Thursday morning in Baltimore for the ETG pre meeting, beginning at 8:00 AM!

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Reposted by Arohan Subramanya

Hyman Lab @hymanlab.bsky.social · 23/01/2025

"Mysterious Blobs Found inside Cells Are Rewriting the Story of How Life Works" Exciting times ahead! www.scientificamerican.com/article/myst...

scientificamerican.com

Mysterious Blobs in Cells Are Changing the Way We Understand Life

Tiny specks called biomolecular condensates are leading to a new understanding of the cell

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