Cell-Penetrating Peptides Corresponding to the Angiotensin II Type 1 Receptor Reduce Receptor Accumulation and Cell Surface Expression and Signaling

Our previous published studies have established the γ-aminobutyric acid (GABA) receptor-associated protein (GABARAP) as a trafficking protein for the angiotensin II type 1A receptor (AT(1)R). GABARAP overexpression increases both AT(1)R protein accumulation and translocation to the plasma membrane. The present study examined the inhibitory effects of decoy peptides on receptor expression and plasma membrane accumulation. The decoy peptides correspond to the AT(1)R cytoplasmic domain located immediately proximal to the 7th transmembrane domain, a region implicated in GABARAP binding. This competitive binding study was designed as a first step toward evaluating the GABARAP:AT(1)R binding interface as a target for reducing AT(1)R trafficking to the plasma membrane.