Membrane cholesterol effect on the 5‐HT2A receptor: Insights into the lipid‐induced modulation of an antipsychotic drug target

Publisher： John Wiley & Sons Inc

E-ISSN： 1470-8744|65|1|29-37

ISSN： 0885-4513

Source： BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY, Vol.65, Iss.1, 2018-01, pp. : 29-37

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

AbstractThe serotonin 5‐hydroxytryptamine 2A (5‐HT2A) receptor is a G‐protein‐coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5‐HT2A receptor dynamics through all‐atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane‐induced alterations of receptor dynamics and points to cholesterol‐induced stabilizing and destabilizing effects on the conformational variability of GPCRs.

Related content

Tph2 gene deletion enhances amphetamine‐induced hypermotility: effect of 5‐HT restoration and role of striatal noradrenaline release

By  

JOURNAL OF NEUROCHEMISTRY (ELECTRONIC), Vol. 135, Iss. 4, 2015-11 ,pp. : 674-685 (12)

John Wiley & Sons Inc

Access to resources Recommend Favorite

Adiponectin Prevents Reduction of Lipid‐Induced Mitochondrial Biogenesis via AMPK/ACC2 Pathway in Chicken Adipocyte

By  

JOURNAL OF CELLULAR BIOCHEMISTRY, Vol. 116, Iss. 6, 2015-06 ,pp. : 1090-1100 (11)

John Wiley & Sons Inc

Access to resources Recommend Favorite

Pantethine Alters Lipid Composition and Cholesterol Content of Membrane Rafts, With Down‐Regulation of CXCL12‐Induced T Cell Migration

By  

JOURNAL OF CELLULAR PHYSIOLOGY, Vol. 230, Iss. 10, 2015-10 ,pp. : 2415-2425 (11)

John Wiley & Sons Inc

Access to resources Recommend Favorite

Discovering the mechanisms underlying serotonin (5‐HT)2A and 5‐HT2C receptor regulation following nicotine withdrawal in rats

By  

JOURNAL OF NEUROCHEMISTRY (ELECTRONIC), Vol. 134, Iss. 4, 2015-08 ,pp. : 704-716 (13)

John Wiley & Sons Inc

Access to resources Recommend Favorite

Kisspeptin1 modulates odorant‐evoked fear response via two serotonin receptor subtypes (5‐HT1A and 5‐HT2) in zebrafish

By  

JOURNAL OF NEUROCHEMISTRY (ELECTRONIC), Vol. 133, Iss. 6, 2015-06 ,pp. : 870-878 (9)

John Wiley & Sons Inc

Access to resources Recommend Favorite