SAP97 Controls the Trafficking and Resensitization of the Beta-1-Adrenergic Receptor through Its PDZ2 and I3 Domains

• DOI: 10.1371/journal.pone.0063379
• Publication Date: 2013-05-16T21:19:21Z
• Authors: Mohammed M. Nooh; Anjaparavanda P. ...; Sung-Jin Kim; Yang K. Xiang; Suleiman W. Bahouth
• Keywords: PDZ domain; HEK 293 cells

Previous studies have determined that the type-1 PDZ sequence at extreme carboxy-terminus of ß1-adrenergic receptor (ß1-AR) binds SAP97 and AKAP79 to organize a scaffold involved in trafficking ß1-AR. In this study we focused on characterizing domains were recycling resensitization ß1-AR HEK-293 cells. Using knockdown rescue strategy, PDZ-deletion mutants containing PDZ2 rescued Among three PDZs SAP97, displayed highest affinity binding Expression isolated PDZ2, but not other PDZs, inhibited by destabilizing macromolecular complex functional addition its contains protein interacting domains, such as I3 SRC homology-3 (SH3) domain, which AKAP79. Deletion from (ΔI3-SAP97) did affect However, ΔI3-SAP97 could because it failed incorporate AKAP79/PKA into SAP97-ß1-AR complex. Therefore, bipartite is necessary for SAP97-mediated effects recycling, externalization These data establish prominent role organizing receptosome connecting signaling networks.