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Deprecated: Implicit conversion from float 245.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 J+Biol+Chem 2016 ; 291 (38): 20232-46 Nephropedia Template TP
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S-Palmitoylation of a Novel Site in the ?2-Adrenergic Receptor Associated with a Novel Intracellular Itinerary* #MMPMID27481942
Adachi N; Hess DT; McLaughlin P; Stamler JS
J Biol Chem 2016[Sep]; 291 (38): 20232-46 PMID27481942show ga
We report here that a population of human ?2-adrenergic receptors (?2AR), a canonical G protein-coupled receptor, traffics along a previously undescribed intracellular itinerary via the Golgi complex that is associated with the sequential S-palmitoylation and depalmitoylation of a previously undescribed site of modification, Cys-265 within the third intracellular loop. Basal S-palmitoylation of Cys-265 is negligible, but agonist-induced ?2AR activation results in enhanced S-palmitoylation, which requires phosphorylation by the cAMP-dependent protein kinase of Ser-261/Ser-262. Agonist-induced turnover of palmitate occurs predominantly on Cys-265. Cys-265 S-palmitoylation is mediated by the Golgi-resident palmitoyl transferases zDHHC9/14/18 and is followed by depalmitoylation by the plasma membrane-localized acyl-protein thioesterase APT1. Inhibition of depalmitoylation reveals that S-palmitoylation of Cys-265 may stabilize the receptor at the plasma membrane. In addition, ?2AR S-palmitoylated at Cys-265 are selectively preserved under a sustained adrenergic stimulation, which results in the down-regulation and degradation of ?AR. Cys-265 is not conserved in ?1AR, and S-palmitoylation of Cys-265 may thus be associated with functional differences between ?2AR and ?1AR, including relative resistance of ?2AR to down-regulation in multiple pathophysiologies. Trafficking via the Golgi complex may underlie new roles in G protein-coupled receptor biology.