title: DJ-1 associates with synaptic membranes.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons. Although many reports have suggested that genetic factors are implicated in the pathogenesis of PD, molecular mechanisms underlying selective dopaminergic neuronal degeneration remain unknown. DJ-1 is a causative gene for autosomal recessive form of PARK7-linked early-onset PD. A number of studies have demonstrated that exogenous DJ-1 localizes within mitochondria and the cytosol, and functions as a molecular chaperone, as a transcriptional regulator, and as a cell protective factor against oxidative stress. However, the precise subcellular localization and function of endogenous DJ-1 are not well known. The mechanisms by which mutations in DJ-1 contributes to neuronal degeneration also remain poorly understood. Here we show by immunocytochemistry that DJ-1 distributes to the cytosol and membranous structures in a punctate appearance in cultured cells and in primary neurons obtained from mouse brain. Interestingly, DJ-1 colocalizes with the Golgi apparatus proteins GM130 and the synaptic vesicle proteins such as synaptophysin and Rab3A. Förster resonance energy transfer analysis revealed that a small portion of DJ-1 interacts with synaptophysin in living cells. Although the wild-type DJ-1 protein directly associates with membranes without an intermediary protein, the pathogenic L166P mutation of DJ-1 exhibits less binding to synaptic vesicles. These results indicate that DJ-1 associates with membranous organelles including synaptic membranes to exhibit its normal function.
authors.affiliation: Department of Neurology, Juntendo University School of Medicine, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Usami
authors.forename: Taku
authors.initials: T
authors.lastname: Hatano
authors.forename: Satoshi
authors.initials: S
authors.lastname: Imai
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Kubo
authors.forename: Shigeto
authors.initials: S
authors.lastname: Sato
authors.forename: Shinji
authors.initials: S
authors.lastname: Saiki
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Fujioka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Sato
authors.forename: Manabu
authors.initials: M
authors.lastname: Funayama
authors.forename: Hiroto
authors.initials: H
authors.lastname: Eguchi
authors.forename: Kaori
authors.initials: K
authors.lastname: Shiba
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Ariga
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009447:Neuroblastoma; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D013570:Synaptic Membranes / Q000378:metabolism*
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D054464:Peroxiredoxins; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; D000071617:Protein Deglycase DJ-1