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Konstantin Glebov"Functional significance of palmitoylation of the serotonin receptors for intracellular signaling and its localization"

Abstract :

Serotonin (5-HT) is one of the major neurotransmitters in animals.
In the human central nervous system, 5-HT is involved in a variety of processes, including the regulation of feeding behavior, mood, perception, anxiety, aggression and pain. In mammals, the function of 5-HT is mediated through seven classes of serotonin receptors. Six of these classes are G-protein coupled receptors (GPCRs), and one, the 5-HT3 receptor, is a ligand-gated ion channel.
It has been shown that posttranslational modification, such as palmitoylation, affects several aspects of GPCR function: the efficiency and selectivity of G-protein coupling, receptor phosphorylation and desensitization, endocytosis, and trafficking to the plasma membrane. Using palmitoylation deficient mutants of two serotonin receptors 5-HT1 and 5-HT4 we show that: (i) palmitoylation can be responsible for formation of a specific conformational state of the intracellular part of the receptor, which promotes better interaction between receptor and G-protein; (ii) palmitoylation facilitates receptor trafficking to membrane subdomains (lipid rafts) where receptor interacts with other signaling proteins.

Selected publications

1. “Palmitoylation of the 5-Hydroxytryptamine4a Receptor Regulates Receptor Phosphorylation, Desensitization, and ß-Arrestin-Mediated Endocytosis” E. Ponimaskin, A. Dumuis, F. Gaven, G. Barthet, M. Heine, K. Glebov, D. W. Richter, and M. Oppermann. Molecular Pharmacology Feb. 2, 2005
2. “Localization of the 5-HT1A receptor in lipid rafts is important for the receptor interaction with heterotrimeric Gi protein and is dependent on receptor palmitoylation” U. Renner#, K. Glebov#, et al. Submitted to Mol. Biol. Cell, # Authors contribute equally.

Nathalie Sans