title: Sphingolipids modulate the function of human serotonin1Areceptors: Insights from sphingolipid-deficient cells.
abstract: Sphingolipids are essential components of eukaryotic cell membranes and are known to modulate a variety of cellular functions. It is becoming increasingly clear that membrane lipids play a crucial role in modulating the function of integral membrane proteins such as G protein-coupled receptors (GPCRs). In this work, we utilized LY-B cells, that are sphingolipid-auxotrophic mutants defective in sphingolipid biosynthesis, to monitor the role of cellular sphingolipids in the function of an important neurotransmitter receptor, the serotonin1Areceptor. Serotonin1Areceptors belong to the family of GPCRs and are implicated in behavior, development and cognition. Our results show that specific ligand binding and G-protein coupling of the serotonin1Areceptor exhibit significant enhancement under sphingolipid-depleted conditions, which reversed to control levels upon replenishment of cellular sphingolipids. In view of the reported role of sphingolipids in neuronal metabolism and pathogenesis of several neuropsychiatric disorders, exploring the role of serotonin1Areceptors under conditions of defective sphingolipid metabolism assumes relevance, and could contribute to our overall understanding of such neuropsychiatric disorders. This article is part of a Special Issue entitled: Lipid order/lipid defects and lipid-control of protein activity edited by Dirk Schneider.
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Md
authors.initials: M
authors.lastname: Jafurulla
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Suman
authors.initials: S
authors.lastname: Bandari
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Pucadyil
authors.affiliation: CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India. Electronic address: amit@ccmb.res.in.
authors.forename: Amitabha
authors.initials: A
authors.lastname: Chattopadhyay
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism; D003412:Cricetulus; D017353:Gene Deletion; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics* / Q000378:metabolism; D051102:Serine C-Palmitoyltransferase / Q000172:deficiency / Q000235:genetics; D058825:Serotonin 5-HT1 Receptor Agonists / Q000378:metabolism / Q000494:pharmacology*; D015398:Signal Transduction; D013110:Sphingosine / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D008563:Membrane Lipids; D058825:Serotonin 5-HT1 Receptor Agonists; C054562:yellow fluorescent protein, Bacteria; D044282:Receptor, Serotonin, 5-HT1A; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D051102:Serine C-Palmitoyltransferase; D013110:Sphingosine
keywords: GPCR; LY-B cells; Lipid-protein interactions; Serotonin(1A) receptor; Sphingolipids