Scribble influences cyst formation in autosomal-dominant polycystic kidney disease by regulating Hippo signaling pathway

Polarity complexes, including the PAR (Partitioning-defective), CRB (Crumbs) and SCRIB (Scribble) complexes, are required for the physiologic establishment, stabilization, and maintenance of a functional apical-basolateral polarity. Inactivation of some of the polarity complexes results in cystic kidneys, and apical–basolateral polarity defects are commonly observed in autosomal-dominant polycystic kidney disease (ADPKD); however, little is known about the role that polarity complexes play in ADPKD. Here, we demonstrate that Scribble, a core protein of the SCRIB complex, is down-regulated in ADPKD cell lines and the zebrafish model of this disease (pkd2 morphants). Overexpression of Scribble could reduce cyst formation in pkd2 morphants, and loss of scrib led to a dilated pronephric duct in zebrafish. Furthermore, the Hippo signaling pathway was inactivated in scrib mutants and pkd2 morphants in which Yes-associated protein (YAP), which is physiologically located in the cytoplasm, was translocated to the ...