Figure 11.

A summary of the findings in the present study. Upon the withdrawal of vasopressin stimulation, AQP2 is internalized into early endosomes for sorting. At the early endosome, AQP2 could be entered (1) to the recycling pathways either via the trans-Golgi network or directly to the plasma membrane, leading to AQP2 expression in the apical plasma membrane of the collecting duct principal cells in the kidney or (2) to the lysosomal pathway for degradation, leading to downregulation of AQP2 in the plasma membrane and the cells [1,2,5,6,7,8,9,12,61]. The class I PDZ domain-binding motif (X-[S/T]-X-Φ) in the carboxyl terminus of AQP2 is recognized by PDZ domain-containing proteins, e.g., SNX27. SNX27 is bound to the Vps26 of retromer complex subunits and concurrently binds to the PDZ ligand in its cargo proteins (AQP2); thereby, it could be involved in the recycling of AQP2 into the plasma membrane. The retromer complex is involved in the retrograde transport of proteins from endosomes to the trans-Golgi network. Alternatively, AQP2 could be sorted into lysosomes and subjected to lysosomal degradation to a greater extent upon the suppression of SNX27, i.e., SNX27 knockdown or deletion of the PDZ domain and Vps35 depletion [23].