Arohan Subramanya

Surprisingly Complex Assemblies from Low-Complexity Domains | NEJM Drs. Görlich and McKnight have won the 2025 Albert Lasker Award for Basic Medical Research for showing that low-complexity domains of proteins lack structure on their own and yet can form assembled .....

Surprisingly Complex Assemblies from Low-Complexity Domains | New England Journal of Medicine www.nejm.org/doi/full/10....

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)

Thanks so much Pablo!

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

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

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

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/

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-...

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/

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/

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/

…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/

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...

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/

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/

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...

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/

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/

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!

The University of Pittsburgh pauses its Ph.D. admissions process amid research funding uncertainty A spokesperson for the University told WESA Friday that the school has "temporarily paused additional Ph.D. offers of admission," while Pitt works to understand how proposed federal funding cuts could...

The University of Pittsburgh confirmed Friday that there would be no new Ph.D. offers of admission while Pitt works to understand how reduced federal aid could impact the institution.

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

"Mysterious Blobs Found inside Cells Are Rewriting the Story of How Life Works"

Exciting times ahead!

www.scientificamerican.com/article/myst...