RGD Reference Report - DJ-1 associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes. - Rat Genome Database

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DJ-1 associates with lipid rafts by palmitoylation and regulates lipid rafts-dependent endocytosis in astrocytes.

Authors: Kim, Kwang Soo  Kim, Jin Soo  Park, Ji-Young  Suh, Young Ho  Jou, Ilo  Joe, Eun-Hye  Park, Sang Myun 
Citation: Kim KS, etal., Hum Mol Genet. 2013 Dec 1;22(23):4805-17. doi: 10.1093/hmg/ddt332. Epub 2013 Jul 11.
RGD ID: 13462068
Pubmed: PMID:23847046   (View Abstract at PubMed)
DOI: DOI:10.1093/hmg/ddt332   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to lipopolysaccharide  IEP 13462068 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Park7  (Parkinsonism associated deglycase)


Additional Information