Parkin regulates kainate receptors by interacting with the GluK2 subunit.
Nat Commun. 2014-10-15; 5(1):
DOI: 10.1038/ncomms6182
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1. Nat Commun. 2014 Oct 15;5:5182. doi: 10.1038/ncomms6182.
Parkin regulates kainate receptors by interacting with the GluK2 subunit.
Maraschi A(1), Ciammola A(1), Folci A(2), Sassone F(1), Ronzitti G(3),
Cappelletti G(4), Silani V(5), Sato S(6), Hattori N(6), Mazzanti M(4),
Chieregatti E(3), Mulle C(7), Passafaro M(2), Sassone J(1).
Author information:
(1)IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory of
Neuroscience, Cusano Milanino, 20095 Milan, Italy.
(2)CNR Institute of Neuroscience, Department of BIOMETRA, University of Milan,
20129 Milan, Italy.
(3)Department of Neuroscience and Brain Technologies, Istituto Italiano di
Tecnologia, 16163 Genova, Italy.
(4)Department of Biosciences, Università degli Studi di Milano, 20122 Milan,
Italy.
(5)1] IRCCS Istituto Auxologico Italiano, Department of Neurology and Laboratory
of Neuroscience, Cusano Milanino, 20095 Milan, Italy [2] ‘Dino Ferrari’ Center,
Department of Pathophysiology and Transplantation, Università degli Studi di
Milano, 20122 Milan, Italy.
(6)Department of Neurology, Juntendo University School of Medicine, 113-8421
Tokyo, Japan.
(7)Interdisciplinary Institute for Neuroscience, CNRS UMR 5297, University of
Bordeaux, 33000 Bordeaux, France.
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.
DOI: 10.1038/ncomms6182
PMCID: PMC4218952
PMID: 25316086 [Indexed for MEDLINE]