Molecular interaction between parkin and PINK1 in mammalian neuronal cells

Ji Won Um, Christine Stichel-Gunkel, Hermann Lübbert, Gwang Lee, Kwang Chul Chung

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56 Citations (Scopus)

Abstract

Parkinson's disease (PD) is characterized by the deterioration of dopaminergic neurons in the pars compacta of substantia nigra and the formation of intraneuronal protein inclusions. The etiology of PD is not known, but the recent identification of several mutation genes in familial PD has provided a rich understanding of the molecular mechanisms of PD pathology. Mutations in PTEN-induced putative kinase 1 (PINK1) and parkin are linked to early-onset autosomal recessive forms of familial PD. Here we show molecular and functional interactions between parkin and PINK1. Parkin selectively binds to PINK1 and upregulates PINK1 levels. In addition, PINK1 reduces the solubility of parkin, which induces the formation of microtubule-dependent cytoplasmic aggresomes. Our findings reveal that parkin and PINK1 affect each other's stability, solubility and tendency to form aggresomes, and have important implications regarding the formation of Lewy bodies.

Original languageEnglish
Pages (from-to)421-432
Number of pages12
JournalMolecular and Cellular Neuroscience
Volume40
Issue number4
DOIs
Publication statusPublished - 2009 Apr

Bibliographical note

Funding Information:
We thank K. Tanaka, H. Rhim, M.R. Cookson, M. Mouradian, W.S. Park, P.M. Snyder, and T.H. Lee for providing plasmids. This study was supported by grants from the Brain Research Center of the 21st Century Frontier Research Program Technology (M103KV010011-06K2201-01110 to K.C.C.) and from the Korea Science and Engineering Foundation (KOSEF) through National Research Laboratory Program (R04-2007-000-20014-0 to K.C.C.) funded by Ministry of Science, Republic of Korea. This work was also partly supported by the KOSEF grant (R11-2007-040-01005-0 and R01-2007-000-20089-0 to K.C.C.), a grant from the Korea Health 21 R and D Project (A080551 to K.C.C.), Ministry of Health and Welfare.

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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