Molecular interaction between parkin and PINK1 in mammalian neuronal cells

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

Research output: Contribution to journalArticle

54 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 1

Fingerprint

Parkinson Disease
Solubility
Lewy Bodies
Mutation
Dopaminergic Neurons
Parkinsonian Disorders
Microtubules
PTEN-induced putative kinase
Up-Regulation
Pathology
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Um, Ji Won ; Stichel-Gunkel, Christine ; Lübbert, Hermann ; Lee, Gwang ; Chung, Kwang Chul. / Molecular interaction between parkin and PINK1 in mammalian neuronal cells. In: Molecular and Cellular Neuroscience. 2009 ; Vol. 40, No. 4. pp. 421-432.
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Molecular interaction between parkin and PINK1 in mammalian neuronal cells. / Um, Ji Won; Stichel-Gunkel, Christine; Lübbert, Hermann; Lee, Gwang; Chung, Kwang Chul.

In: Molecular and Cellular Neuroscience, Vol. 40, No. 4, 01.04.2009, p. 421-432.

Research output: Contribution to journalArticle

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AB - 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.

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