Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Maraschi, A; 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.
Parkin regulates kainate receptors by interacting with the GluK2 subunit.
Nat Commun. 2014; 5(3):5182-5182
Doi: 10.1038/ncomms6182
[OPEN ACCESS]
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Folci Alessandra Chiara
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cell Membrane - genetics
- Disease Models, Animal -
- Female -
- Humans -
- Mice -
- Mice, Transgenic -
- Neurons - metabolism
- Parkinsonian Disorders - genetics
- Protein Binding -
- Rats -
- Receptors, Kainic Acid - genetics
- Ubiquitin-Protein Ligases - genetics