Determination of protein-bound palmitate turnover rates using a three-compartment model that formally incorporates [3H]palmitate recycling.

The observation that the palmitoylation state of certain proteins can be biologically modulated led to the proposal that it could, much like phosphorylation, be an important dynamic regulator of protein function. However, based on single-phase exponential decay analysis of data from [(3)H]palmitate pulse/chase experiments, the measured protein-bound palmitate turnover rates were often found to be too slow to account for rapid physiological responses. This paper reports that exponential decay does not adequately describe the results of such experiments because it fails to account for the recycling of [(3)H]palmitate from cellular lipids to palmitoyl CoA.

Phosphorylation-independent desensitization of GABA(B) receptor by GRK4.

Agonist-promoted desensitization of the heterodimeric metabotropic GABA(B) receptor was investigated. Whereas no desensitization was observed in HEK293 cells heterologously expressing the receptor, GABA and the synthetic agonist baclofen induced a robust desensitization in cerebellar granule cells endogenously expressing the receptor. Taking advantage of this cell-specific desensitization phenotype, we identified GRK4 as the kinase involved in the neuronal desensitization.

Role of palmitoylation/depalmitoylation reactions in G-protein-coupled receptor function.

G-protein-coupled receptors (GPCRs) constitute one of the largest protein families in the human genome. They are subject to numerous post-translational modifications, including palmitoylation. This review highlights the dynamic nature of palmitoylation and its role in GPCR expression and function.