title: Light induces Fos expression via extracellular signal-regulated kinases 1/2 in melanopsin-expressing PC12 cells.
abstract: The photopigment melanopsin is expressed in a subtype of mammalian ganglion cells in the retina that project to the circadian clock in the hypothalamic suprachiasmatic nucleus to mediate non-visual light information. Melanopsin renders these retinal ganglion cells intrinsically photosensitive and the cells respond to light by a membrane depolarization and induction of the immediate early response gene Fos. Previous studies showed that the light activated melanopsin-induced signaling, the phototransduction, leading to depolarization of the membrane resembles the invertebrate opsins, which involves a Galpha(q/11) coupled phospholipase C activation. However, the signaling proteins mediating melanopsin-induced Fos expression are unresolved. In this study, we examined the phototransduction leading to Fos expression in melanopsin-transfected PC12 cells. A pivotal role of the extracellular signal-regulated protein kinase 1/2 (ERK1/2) was found as pharmacological blockage of this kinase suppressed the light-induced Fos expression. Illumination increased the inositol phosphate turnover and induced phosphorylation of ERK1/2 and p38 but not the c-Jun N-terminal kinase. The Galpha(q/11) protein inhibitor YM254890 attenuated these intracellular light responses. Our data strongly indicate that Galpha(q/11)-mediated ERK1/2 activation is essential for expression of Fos upon illumination of melanopsin-expressing PC12 cells.
authors: Department of Clinical Biochemistry, Faculty of Health Sciences, Bispebjerg Hospital, University of Copenhagen, Copenhagen NV, Denmark.
authors: Marie-Louise
authors: ML
authors: Moldrup
authors: Birgitte
authors: B
authors: Georg
authors: Birgitte
authors: B
authors: Falktoft
authors: Rikke
authors: R
authors: Mortensen
authors: Jakob Lerche
authors: JL
authors: Hansen
authors: Jan
authors: J
authors: Fahrenkrug
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D007295:Inositol Phosphates / Q000378:metabolism; D008027:Light; D016761:Oncogene Proteins v-fos / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D051381:Rats; D017299:Rod Opsins / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014162:Transfection / Q000379:methods; D000099210:Melanopsin
chemical_list: D004791:Enzyme Inhibitors; D048049:Extracellular Signal-Regulated MAP Kinases; D007295:Inositol Phosphates; D016761:Oncogene Proteins v-fos; D017299:Rod Opsins; D000099210:Melanopsin