FIGURE 7:

Model WW-PLEKHA- and PDZD11-regulated ATP7A trafficking. Schematic model and graphical legend describing the localization of the indicated proteins and the implication of WW-PLEKHAs and PDZD11 in the anterograde trafficking of ATP7A in absorptive polarized epithelial cells (MDCK) either in basal Cu (left) or in elevated Cu (right), based on IF results shown in Figures 3 and 4 and Supplemental Figures S6 and S7. The lateral plasma membrane (PM) and the apico-lateral AJ are shown on the left. PLEKHA7 is exclusively localized at the AJ/ZA. Under basal copper (Basal Cu, left), few ATP7A-containing membrane vesicles cycle between the plasma membrane and trans-Golgi network (TGN), and most ATP7A is in the TGN. With elevated copper (Elevated Cu, right), ATP7A-containing membrane vesicles are trafficked to the cell periphery along microtubule (MT) tracks and are tethered to the apical lateral and basal PM by the WW-PLEKHA-PDZD11 complexes. Copper chaperones, transporters, adaptors, and signaling proteins involved in copper homeostasis (La Fontaine and Mercer, 2007; Lutsenko et al., 2007; Polishchuk and Lutsenko, 2013) are not shown for the sake of simplicity.