Role of AJC in umbrella cell function and dysfunction

The project aims to understand how the AJC maintains continuity during cyclical bladder filling and voiding, its organization and the function of its cytoskeleton in these events, and how it senses tension and responds to pathological intravesical pressures. Specific experiments include: (1) using a biaxial stretching device and live-cell image analysis to determine if strain triggers exocytosis/endocytosis of junction-associated proteins and if blocking AJC expansion perturbs urothelial barrier function; (2) deciphering the function and organization of the AJC-associated cytoskeleton using super-resolution confocal imaging and electron microscopy, and assessing formin-driven actin polymerization; and (3) using tension sensors to determine if AJC transmembrane proteins sense force and if signaling pathways are activated in response to partial bladder outlet obstruction (PBOO).