RRC ID 51655
Author Hossain MS, Mineno K, Katafuchi T.
Title Neuronal Orphan G-Protein Coupled Receptor Proteins Mediate Plasmalogens-Induced Activation of ERK and Akt Signaling.
Journal PLoS One
Abstract The special glycerophospholipids plasmalogens (Pls) are enriched in the brain and reported to prevent neuronal cell death by enhancing phosphorylation of Akt and ERK signaling in neuronal cells. Though the activation of Akt and ERK was found to be necessary for the neuronal cells survival, it was not known how Pls enhanced cellular signaling. To answer this question, we searched for neuronal specific orphan GPCR (G-protein coupled receptor) proteins, since these proteins were believed to play a role in cellular signal transduction through the lipid rafts, where both Pls and some GPCRs were found to be enriched. In the present study, pan GPCR inhibitor significantly reduced Pls-induced ERK signaling in neuronal cells, suggesting that Pls could activate GPCRs to induce signaling. We then checked mRNA expression of 19 orphan GPCRs and 10 of them were found to be highly expressed in neuronal cells. The knockdown of these 10 neuronal specific GPCRs by short hairpin (sh)-RNA lentiviral particles revealed that the Pls-mediated phosphorylation of ERK was inhibited in GPR1, GPR19, GPR21, GPR27 and GPR61 knockdown cells. We further found that the overexpression of these GPCRs enhanced Pls-mediated phosphorylation of ERK and Akt in cells. Most interestingly, the GPCRs-mediated cellular signaling was reduced significantly when the endogenous Pls were reduced. Our cumulative data, for the first time, suggest a possible mechanism for Pls-induced cellular signaling in the nervous system.
Volume 11(3)
Pages e0150846
Published 2016-1-1
DOI 10.1371/journal.pone.0150846
PII PONE-D-15-45270
PMID 26934370
PMC PMC4775022
MeSH Animals Cell Line Enzyme Activation Extracellular Signal-Regulated MAP Kinases / metabolism* Humans MAP Kinase Signaling System Mice Neurons / metabolism* Phosphorylation Plasmalogens / metabolism* Proto-Oncogene Proteins c-akt / metabolism* Receptors, G-Protein-Coupled / metabolism* Signal Transduction*
IF 2.74
Times Cited 25
Human and Animal Cells MG6(RCB2403)