Fig.6

Model of exocytosis and endocytosis in the absence of pendrin. A: In normal conditions, pendrin transports HCO₃⁻ into the endolymph to maintain pH homeostasis. In addition, the interaction between AP-2 and pendrin may increase the activity of pendrin in the plasma membrane and initiate clathrin-coated vesicle assembly and endocytosis. In the endocytic pathway, molecules are internalized as plasma membrane-derived clathrin-coated vesicles (blue arrows). Also, clathrin-coated vesicles carry cargo from the trans-Golgi-network and reach the plasma membrane through secretory granules (black arrows). ANXA1 in exosomes is secreted from the SCs. SCs and IMCs interact through exosomes. B: The interruption of the interaction between pendrin and AP-2 affects the trafficking and activity of pendrin and lowers the pH of endolymph. In addition, AP-2 increases in PDCs through increased endocytosis within the cell. In the absence of pendrin, endolymph pH drops from 7.5 to 7.1. ANXA1 in exosomes is released from the SCs and translocated and internalized in the IMCs through exocytosis (E, endolymph; EP, endolymph potential; IMC, intermediate cell; PDC, pendrin-expressing cell; SC, spindle cell)