Endocytosis under pressure

Endocytosis under pressure

Cells convert mechanical forces in their environment into downstream biochemical processes through the mechanism of mechanotransduction. The forces that cells may undergo in a biological context may manifest in the forms of membrane stretch, shear stress, osmotic pressure, cell texture and stiffness. Transduction of forces results in a number of physiological processes, e.g. cell differentiation, migration, apoptosis, transcription, and change in membrane potential.

The Laboratory of Cell Physiology studies the role of mechanosensitive ion channels such as Piezo or TRPV4 ("Transient Receptor Potential type vaniloid 4") in different organs, especially in the nervous system and in the kidney.

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. Doctor Roberta Gualdani and Professor Philippe Gailly's team 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. In a paper published this October 13th in Science Signaling (https://stke.sciencemag.org/content/13/653/eabc6967), they show that experimental manipulations mimicking nephropathies and increasing 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.

Article published in Science Signaling by our colleagues: Roberta Gualdani, François Seghers, Xavier Yerna, Olivier Schakman, Nicolas Tajeddine, Younès Achouri, Fadel Tissir, Olivier Devuyst, Philippe Gailly.

Links to access documents online:

Summary: http://stke.sciencemag.org/cgi/content/summary/sigtrans;13/653/eabc6967?ijkey=Z8eQvwkyjAe8s&keytype=ref&siteid=sigtrans

Abstract: http://stke.sciencemag.org/cgi/content/abstract/sigtrans;13/653/eabc6967?ijkey=Z8eQvwkyjAe8s&keytype=ref&siteid=sigtrans

Reprint: http://stke.sciencemag.org/cgi/reprint/sigtrans;13/653/eabc6967?ijkey=Z8eQvwkyjAe8s&keytype=ref&siteid=sigtrans

Full text: http://stke.sciencemag.org/cgi/content/full/sigtrans;13/653/eabc6967?ijkey=Z8eQvwkyjAe8s&keytype=ref&siteid=sigtrans