Parkin regulates kainate receptors by interacting with the GluK2 subunit

Although loss-of-function mutations in the PARK2 gene, the gene that encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, the responsible molecular mechanisms remain unclear. Evidence suggests that a loss of parkin dysregulates excitatory synapses. Here we show that parkin in...

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Main Authors:	Maraschi, AnnaMaria, Ciammola, Andrea, Folci, Alessandra, Sassone, Francesca, Ronzitti, Giuseppe, Cappelletti, Graziella, Silani, Vincenzo, Sato, Shigeto, Hattori, Nobutaka, Mazzanti, Michele, Chieregatti, Evelina, Mulle, Christophe, Passafaro, Maria, Sassone, Jenny
Format:	Online
Language:	English
Published:	Nature Pub. Group 2014
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218952/

id	pubmed-4218952
recordtype	oai_dc
spelling	pubmed-42189522014-11-06 Parkin regulates kainate receptors by interacting with the GluK2 subunit Maraschi, AnnaMaria Ciammola, Andrea Folci, Alessandra Sassone, Francesca Ronzitti, Giuseppe Cappelletti, Graziella Silani, Vincenzo Sato, Shigeto Hattori, Nobutaka Mazzanti, Michele Chieregatti, Evelina Mulle, Christophe Passafaro, Maria Sassone, Jenny Article Although loss-of-function mutations in the PARK2 gene, the gene that encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, the responsible molecular mechanisms remain unclear. Evidence suggests that a loss of parkin dysregulates excitatory synapses. Here we show that parkin interacts with the kainate receptor (KAR) GluK2 subunit and regulates KAR function. Loss of parkin function in primary cultured neurons causes GluK2 protein to accumulate in the plasma membrane, potentiates KAR currents and increases KAR-dependent excitotoxicity. Expression in the mouse brain of a parkin mutant causing autosomal recessive juvenile parkinsonism results in GluK2 protein accumulation and excitotoxicity. These findings show that parkin regulates KAR function in vitro and in vivo, and suggest that KAR upregulation may have a pathogenetic role in parkin-related autosomal recessive juvenile parkinsonism. Nature Pub. Group 2014-10-15 /pmc/articles/PMC4218952/ /pubmed/25316086 http://dx.doi.org/10.1038/ncomms6182 Text en Copyright © 2014, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Maraschi, AnnaMaria Ciammola, Andrea Folci, Alessandra Sassone, Francesca Ronzitti, Giuseppe Cappelletti, Graziella Silani, Vincenzo Sato, Shigeto Hattori, Nobutaka Mazzanti, Michele Chieregatti, Evelina Mulle, Christophe Passafaro, Maria Sassone, Jenny
spellingShingle	Maraschi, AnnaMaria Ciammola, Andrea Folci, Alessandra Sassone, Francesca Ronzitti, Giuseppe Cappelletti, Graziella Silani, Vincenzo Sato, Shigeto Hattori, Nobutaka Mazzanti, Michele Chieregatti, Evelina Mulle, Christophe Passafaro, Maria Sassone, Jenny Parkin regulates kainate receptors by interacting with the GluK2 subunit
author_facet	Maraschi, AnnaMaria Ciammola, Andrea Folci, Alessandra Sassone, Francesca Ronzitti, Giuseppe Cappelletti, Graziella Silani, Vincenzo Sato, Shigeto Hattori, Nobutaka Mazzanti, Michele Chieregatti, Evelina Mulle, Christophe Passafaro, Maria Sassone, Jenny
author_sort	Maraschi, AnnaMaria
title	Parkin regulates kainate receptors by interacting with the GluK2 subunit
title_short	Parkin regulates kainate receptors by interacting with the GluK2 subunit
title_full	Parkin regulates kainate receptors by interacting with the GluK2 subunit
title_fullStr	Parkin regulates kainate receptors by interacting with the GluK2 subunit
title_full_unstemmed	Parkin regulates kainate receptors by interacting with the GluK2 subunit
title_sort	parkin regulates kainate receptors by interacting with the gluk2 subunit
description	Although loss-of-function mutations in the PARK2 gene, the gene that encodes the protein parkin, cause autosomal recessive juvenile parkinsonism, the responsible molecular mechanisms remain unclear. Evidence suggests that a loss of parkin dysregulates excitatory synapses. Here we show that parkin interacts with the kainate receptor (KAR) GluK2 subunit and regulates KAR function. Loss of parkin function in primary cultured neurons causes GluK2 protein to accumulate in the plasma membrane, potentiates KAR currents and increases KAR-dependent excitotoxicity. Expression in the mouse brain of a parkin mutant causing autosomal recessive juvenile parkinsonism results in GluK2 protein accumulation and excitotoxicity. These findings show that parkin regulates KAR function in vitro and in vivo, and suggest that KAR upregulation may have a pathogenetic role in parkin-related autosomal recessive juvenile parkinsonism.
publisher	Nature Pub. Group
publishDate	2014
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4218952/
_version_	1613151775275089920

Parkin regulates kainate receptors by interacting with the GluK2 subunit

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