title: Isoforms of the Erythropoietin receptor in dopaminergic neurons of the Substantia Nigra.
abstract: Erythropoietin receptor (EpoR) regulates erythrocytes differentiation in blood. In the brain, EpoR has been shown to protect several neuronal cell types from cell death, including the A9 dopaminergic neurons (DA) of the Substantia Nigra (SN). These cells form the nigrostriatal pathway and are devoted to the control of postural reflexes and voluntary movements. Selective degeneration of A9 DA neurons leads to Parkinson's disease. By the use of nanoCAGE, a technology that allows the identification of Transcription Start Sites (TSSs) at a genome-wide level, we have described the promoter-level expression atlas of mouse A9 DA neurons purified with Laser Capture Microdissection (LCM). Here, we identify mRNA variants of the Erythropoietin Receptor (DA-EpoR) transcribed from alternative TSSs. Experimental validation and full-length cDNA cloning is integrated with gene expression analysis in the FANTOM5 database. In DA neurons, the EpoR gene encodes for a N-terminal truncated receptor. Based on STAT5 phosphorylation assays, we show that the new variant of N-terminally truncated EpoR acts as decoy when co-expressed with the full-length form. A similar isoform is also found in human. This work highlights new complexities in the regulation of Erythropoietin (EPO) signaling in the brain.
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Marcuzzi
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy.|Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Zucchelli
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Bertuzzi
authors.affiliation: Department of Health Sciences, University of Eastern Piedmont, Novara, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Santoro
authors.affiliation: Department of Medical and Biological Sciences (DSMB), University of Udine, Udine, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tell
authors.affiliation: Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan.
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: Area of Neuroscience, SISSA, Trieste, Italy.
authors.forename: Stefano
authors.initials: S
authors.lastname: Gustincich
mesh_terms: D000818:Animals; D001483:Base Sequence; D059290:Dopaminergic Neurons / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D061346:Laser Capture Microdissection / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D017467:Receptors, Erythropoietin / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D013378:Substantia Nigra / Q000737:chemistry / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology
chemical_list: D020033:Protein Isoforms; D017467:Receptors, Erythropoietin
keywords: Parkinson's disease; dopaminergic neurons; erythropoietin; erythropoietin receptor