Involvement of PDZ-SAP97 Interactions in Regulating AQP2 Translocation in Response to Vasopressin in LLC-PK1 cells.

Involvement of PDZ-SAP97 Interactions in Regulating AQP2 Translocation in Response to Vasopressin in LLC-PK1 cells. Am J Physiol Renal Physiol. 2019 May 29;: Authors: Nooh MM, Kale A, Bahouth SW Abstract Arginine-vasopressin- (AVP) mediated translocation of aquaporin-2 (AQP2) protein forming water channels from storage vesicles to the membrane of renal collecting ducts is critical for renal conservation of water. The type-1 PDZ-binding motif (PBM) in AQP2 "GTKA" is a critical barcode for its translocation, but its precise role and that of its interacting protein partners in this process remains obscure. We determined that SAP97, a MAGUK protein involved in establishing epithelial cell polarity was an avid binding partner to the PBM of AQP2. The role of the PBM and SAP97 on AQP2 redistribution in response to AVP was assessed in LLC-PK1 renal collecting cells by confocal microscopy and by cell surface biotinylation techniques. These studies indicated that distribution of AQP2 and SAP97 overlapped in the kidneys and in LLC-PK1 cells and that knockdown of SAP97 inhibited the translocation of AQP2 in response to AVP. The binding between AQP2 and SAP97 was mediated by specific interactions between the second PDZ of SAP97 and the PBM of AQP2. Mechanistically, inactivation of the PBM of AQP2, global delocalization of protein kinase A (PKA) or knockdown of SAP97, inhibited AQP2 translocation as well as AVP- and forskolin-mediated phosphorylat...
Source: American Journal of Physiology. Renal Physiology - Category: Physiology Authors: Tags: Am J Physiol Renal Physiol Source Type: research