title: Molecular interaction between parkin and PINK1 in mammalian neuronal cells.
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.
authors.affiliation: Department of Biology, College of Life Science and Biotechnology, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Um
authors.forename: Christine
authors.initials: C
authors.lastname: Stichel-Gunkel
authors.forename: Hermann
authors.initials: H
authors.lastname: Lübbert
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.forename: Kwang Chul
authors.initials: KC
authors.lastname: Chung
mesh_terms: D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism; D011485:Protein Binding; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D000099202:PTEN-Induced Putative Kinase
chemical_list: D011494:Protein Kinases; D011993:Recombinant Fusion Proteins; D044767:Ubiquitin-Protein Ligases; D000099202:PTEN-Induced Putative Kinase; C111567:parkin protein