English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/104222
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


The Parkinson's disease-associated GPR37 receptor-mediated cytotoxicity is controlled by its intracellular cysteine-rich domain

AuthorsGandía, Jorge; Fernández-Dueñas, Victor; Morató, Xavier; Caltabiano, Gianluigi; González-Muñiz, Rosario ; Pardo, Leonardo; Stagljar, Igor; Ciruela, Francisco
Parkinson's disease
orphan receptor
cell surface expression
Issue Date2013
PublisherBlackwell Publishing
CitationJournal of Neurochemistry 125: 362-372 (2013)
AbstractGPR37, also known as parkin-associated endothelin-like receptor (Pael-R), is an orphan G protein-coupled receptor (GPCR) that aggregates intracellularly in a juvenile form of Parkinson's disease. However, little is known about the structure or function of this receptor. Here, in order to better understand the functioning of this receptor, we focused on the GPR37 C-terminal tail, in particular on a cystein-enriched region. Thus, we aimed to reveal the role of these residues on receptor plasma membrane expression and function, and also whether the presence of this cysteine-rich domain is linked to the previously described receptor-mediated cytotoxicity. Interestingly, while the deletion of six cysteine residues within this region did not affect receptor internalization it promoted GPR37 plasma membrane expression and signaling. Furthermore, the removal of the C-terminal cysteine-rich domain protected against GPR37-mediated apoptosis and cell death. Overall, we identified a GPR37 domain, namely the C-terminal tail cysteine-rich domain, which played a critical role in receptor cell surface expression, function and GPR37-mediated cytotoxicity. These results might contribute to better comprehend the pathophysiology (i.e. in Parkinson's disease) of this rather unknown member of the GPCR family. GPR37 is a rather unknown orphan GPCR that in a genetic form of Parkinson's disease accumulates intracellularly and induces neuronal death. In this study, we describe a cystein-rich domain in the C-terminal tail of the receptor that controls its membrane expression and whose absence reduces the GPR37-dependent citotoxic effects on ER stress and cell death.
Identifiersdoi: 10.1111/jnc.12196
issn: 0022-3042
e-issn: 1471-4159
Appears in Collections:(IQM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.