Research ArticlePhysiology

Mechanical activation of TRPV4 channels controls albumin reabsorption by proximal tubule cells

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Science Signaling  13 Oct 2020:
Vol. 13, Issue 653, eabc6967
DOI: 10.1126/scisignal.abc6967

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Endocytosis under pressure

The kidneys filter the blood multiple times a day through structures known as glomeruli, and filtered water, solutes, and proteins such as albumin are reabsorbed by the proximal tubule and returned to the circulation. Kidney damage or disease may result in proteinuria, which can lead to nephropathy if left unchecked. Gualdani et al. found that mechanosensing induced by fluid flow through the proximal tubule activated the cation channel TRPV4 to promote the endocytosis of albumin in tubular epithelial cells and, thus, its retention. Experimental manipulations that increased the permeability of the glomerular filter exacerbated proteinuria in mice lacking TRPV4 globally or specifically in the proximal tubule. Thus, defects in TRPV4-mediated endocytosis may underlie proteinuria, a common symptom of many kidney diseases.

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