Parkin Regulates Kainate Receptors by Interacting with the GluK2 Subunit

Overview

Journal Nat Commun

Specialty Biology

Date 2014 Oct 16

PMID 25316086

Citations 25

Authors

AnnaMaria Maraschi

Andrea Ciammola

Alessandra Folci

Francesca Sassone

Giuseppe Ronzitti

Graziella Cappelletti

Vincenzo Silani

Shigeto Sato

Nobutaka Hattori

Michele Mazzanti

Evelina Chieregatti

Christophe Mulle

Maria Passafaro

Jenny Sassone

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

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