title: DJ-1 associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes.
abstract: Parkinson's disease (PD) is the second most common progressive neurodegenerative disease. Several genes have been associated with familial type PD, providing tremendous insights into the pathogenesis of PD. Gathering evidence supports the view that these gene products may operate through common molecular pathways. Recent reports suggest that many PD-associated gene products, such as α-synuclein, LRRK2, parkin and PINK1, associate with lipid rafts and lipid rafts may be associated with neurodegeneration. Here, we observed that DJ-1 protein also associated with lipid rafts. Palmitoylation of three cysteine residues (C46/53/106) and C-terminal region of DJ-1 were required for this association. Lipopolysaccharide (LPS) induced the localization of DJ-1 into lipid rafts in astrocytes. The LPS-TLR4 signaling was more augmented in DJ-1 knock-out astrocytes by the impairment of TLR4 endocytosis. Furthermore, lipid rafts-dependent endocytosis including the endocytosis of CD14, which play a major role in regulating TLR4 endocytosis was also impaired, but clathrin-dependent endocytosis was not. This study provides a novel function of DJ-1 in lipid rafts, which may contribute the pathogenesis of PD. Moreover, it also provides the possibility that many PD-related proteins may operate through common molecular pathways in lipid rafts.
authors.affiliation: Department of Pharmacology.
authors.forename: Kwang Soo
authors.initials: KS
authors.lastname: Kim
authors.forename: Jin Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Park
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Suh
authors.forename: Ilo
authors.initials: I
authors.lastname: Jou
authors.forename: Eun-Hye
authors.initials: EH
authors.lastname: Joe
authors.forename: Sang Myun
authors.initials: SM
authors.lastname: Park
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003545:Cysteine / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000502:physiology; D054878:Lipoylation; D021962:Membrane Microdomains / Q000378:metabolism*; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D015513:Oncogene Proteins / Q000378:metabolism*; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D051193:Toll-Like Receptors; D054464:Peroxiredoxins; C105131:PARK7 protein, human; C503466:PARK7 protein, mouse; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; D003545:Cysteine