Back

NRBP1 and TSC22D proteins impact distal convoluted tubule physiology through modulation of the WNK pathway

Magana-Avila, G. R.; Carbajal-Contreras, H.; Amnekar, R.; Dite, T.; Tellez-Sutterlin, M.; Garcia-Avila, K.; Marquina-Castillo, B.; Lopez-Saavedra, A.; Vazquez, N.; Rojas-Ortega, E.; Delpire, E.; Ellison, D. H.; Alessi, D. R.; Gamba, G.; Castaneda-Bueno, M.

2024-12-17 physiology
10.1101/2024.12.12.628222 bioRxiv
Show abstract

The With No lysine (WNK) kinases regulate processes such as cell volume and epithelial ion transport through the modulation of Cation Chloride Cotransporters such as the NaCl cotransporter, NCC, present in the distal convoluted tubule (DCT) of the kidney. Recently, the interaction of WNKs with Nuclear Receptor Binding Protein 1 (NRBP1) and Transforming Growth Factor {beta}-Stimulated Clone 22 Domain (TSC22D) proteins was reported. Here we explored the effect of NRBP1 and TSC22Ds on WNK signaling in vitro and in the DCT. TSC22D1.1, TSC22D2, and NRBP1 are localized in DCT WNK bodies, which are cytoplasmic biomolecular condensates associated with WNK activation. In HEK293 cells, long TSC22D isoforms and NRBP1 increase WNK4 activity. DCT-specific NRBP1 knockout mice have reduced NCC phosphorylation and activate a compensatory response. Thus, NRBP1 and long TSC22D proteins are positive modulators of WNK signaling and modulate Na+ reabsorption in the kidney. NRBP1 and TSC22Ds likely influence WNK signaling in other tissues, impacting various physiological processes. TeaserThe pseudokinase NRBP1 and its associated TSC22D proteins modulate WNK kinases to regulate sodium reabsorption in the kidney.

Matching journals

The top 6 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.