@article{b0a160d232fc4278a017651c3dc6b42e,
title = "Attenuated palmitoylation of serotonin receptor 5-HT1A affects receptor function and contributes to depression-like behaviors",
abstract = "The serotonergic system and in particular serotonin 1A receptor (5-HT1AR) are implicated in major depressive disorder (MDD). Here we demonstrated that 5-HT1AR is palmitoylated in human and rodent brains, and identified ZDHHC21 as a major palmitoyl acyltransferase, whose depletion reduced palmitoylation and consequently signaling functions of 5-HT1AR. Two rodent models for depression-like behavior show reduced brain ZDHHC21 expression and attenuated 5-HT1AR palmitoylation. Moreover, selective knock-down of ZDHHC21 in the murine forebrain induced depression-like behavior. We also identified the microRNA miR-30e as a negative regulator of Zdhhc21 expression. Through analysis of the post-mortem brain samples in individuals with MDD that died by suicide we find that miR-30e expression is increased, while ZDHHC21 expression, as well as palmitoylation of 5-HT1AR, are reduced within the prefrontal cortex. Our study suggests that downregulation of 5-HT1AR palmitoylation is a mechanism involved in depression, making the restoration of 5-HT1AR palmitoylation a promising clinical strategy for the treatment of MDD.",
keywords = "PREFRONTAL CORTEX, MAJOR DEPRESSION, 5-HYDROXYTRYPTAMINE(1A) RECEPTOR, PROTEIN PALMITOYLATION, CODING REGION, MICE LACKING, 1A BINDING, STRESS, EXPRESSION, MICRORNAS",
author = "Nataliya Gorinski and Monika Bijata and Sonal Prasad and Alexander Wirth and Galil, {Dalia Abdel} and Andre Zeug and Darla Bazovkina and Elena Kondaurova and Elizabeth Kulikova and Tatiana Ilchibaeva and Monika Zareba-Koziol and Francesco Papaleo and Diego Scheggia and Gaga Kochlamazashvili and Alexander Dityatev and Ian Smyth and Adam Krzystyniak and Jakub Wlodarczyk and Richter, {Diethelm W.} and Tatyana Strekalova and Stephan Sigrist and Claudia Bang and Lisa Hobuss and Jan Fiedler and Thomas Thum and Naumenko, {Vladimir S.} and Ghanshyam Pandey and Evgeni Ponimaskin",
note = "Funding Information: We thank Dr. Nicholas Davis for his help in establishing the ABE assay and Dr. Masaki Fukata for providing ZDHHC clones. We thank Elena Zakharova and Viktoria Ravkina for technical support and Dr. Christo Goridis and Dr. Martina Muehlenhoff for providing anti-NCAM antibodies. This study was supported by the Deutsche For-schungsgemeinschaft (DFG) grant PO732 to E.P.; by the Basic Research project #0324–2019–0041 and Russian Scientific Foundation (grant No 19-15-00025) to V.S.N.; and by “5–100” Russian Academic Excellence Project, NARSAD and the Brain and Behavior Research Fund, Young Investigator Award to T.S. T.T. was supported by a Consolidator ERC grant from the European Union, and T.T. and E.P. were supported by the REBIRTH Excellence cluster. J.W., A.K., and M.Z. acknowledge the National Science Centre grants: UMO-2017/26/E/NZ4/00637. M.B. has been partially supported by the Polish Ministry of Science (1342/1/MOB/IV/15/2016/0). Publisher Copyright: {\textcopyright} 2019, The Author(s).",
year = "2019",
month = sep,
day = "2",
doi = "10.1038/s41467-019-11876-5",
language = "English",
volume = "10",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}