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Mechanosensation of the polycystin ion-channels and their role in vascular pathology

Final Activity Report Summary - VASCULAR POLYCYSTINS (Mechanosensation of the polycystin ion-channels and their role in vascular pathology)

Mechanotransduction underlies major physiological functions such as the sense of touch, hearing or arterial pressure sensing. It was suggested that the polycystin complex TRPP1/TRPP2, mutated in autosomal dominant polycystic kidney disease, acted as a flow sensor in the primary cilium of renal and endothelial cells. However, the way in which polycystins contributed to cellular mechanosensitivity remained obscure. Our study showed that, surprisingly, TRPP2, through the actin cross-linking protein filamin A, inhibited stretch-activated ion channels and impaired the arterial myogenic response to intraluminal pressure. This specific effect was reversed by co-expression with TRPP1, indicating that the TRPP1/TRPP2 ratio regulated pressure sensing.