title: A product of the human gene adjacent to parkin is a component of Lewy bodies and suppresses Pael receptor-induced cell death.
abstract: Parkin, a RING-type ubiquitin ligase, is the product of the gene responsible for autosomal recessive juvenile parkinsonism. A reverse strand gene located upstream of the parkin gene in the human genome has been identified. The gene product, termed Glup/PACRG, forms a large molecular chaperone complex containing heat shock proteins 70 and 90 and chaperonin components. Glup suppressed cell death induced by accumulation of unfolded Pael receptor (Pael-R), a substrate of Parkin. On the other hand, Glup facilitated the formation of inclusions consisting of Pael-R, molecular chaperones, protein degradation molecules, and Glup itself, when proteasome is inhibited. Glup knockdown attenuated the formation of Pael-R inclusions, which resulted in the promotion of cell death with extensive vacuolization. Moreover, Glup turned out to be a component of Lewy bodies in Parkinson's disease cases. These data suggest that Glup may play an important role in the formation of Lewy bodies and protection of dopaminergic neurons against Parkinson's disease.
authors.affiliation: Laboratory for Motor System Neurodegeneration, RIKEN Brain Science Institute, Saitama 351-0198, Japan.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Imai
authors.forename: Mariko
authors.initials: M
authors.lastname: Soda
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Murakami
authors.forename: Mikio
authors.initials: M
authors.lastname: Shoji
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
mesh_terms: D001483:Base Sequence; D016923:Cell Death; D002460:Cell Line; D003546:Cysteine Endopeptidases; D018840:HSP70 Heat-Shock Proteins; D006801:Humans; D002479:Inclusion Bodies; D016631:Lewy Bodies / Q000737:chemistry*; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D046988:Proteasome Endopeptidase Complex; D011506:Proteins / Q000378:metabolism / Q000502:physiology*; D043562:Receptors, G-Protein-Coupled / Q000502:physiology*; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: C480827:GPR37 receptor, human; D018840:HSP70 Heat-Shock Proteins; D008840:Microfilament Proteins; D018832:Molecular Chaperones; D009097:Multienzyme Complexes; C471711:PACRG protein, human; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex