Parkin regulates kainate receptors by interacting with the GluK2 subunit

Anna Maria 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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number5182
JournalNature Communications
Volume5
DOIs
Publication statusPublished - 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Chemistry(all)
  • Physics and Astronomy(all)
  • Medicine(all)

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  • Cite this

    Maraschi, A. M., Ciammola, A., Folci, A., Sassone, F., Ronzitti, G., Cappelletti, G., Silani, V., Sato, S., Hattori, N., Mazzanti, M., Chieregatti, E., Mulle, C., Passafaro, M., & Sassone, J. (2014). Parkin regulates kainate receptors by interacting with the GluK2 subunit. Nature Communications, 5, [5182]. https://doi.org/10.1038/ncomms6182