DJ-1 regulates the endocytosis via Flot-1, the component of lipid rafts
Kim, Jin-Mo; Choi, Yuree; Kang, Seo-Jun; Park, Sang Myun
Department of Pharmacology
Parkinson's disease (PD) is a neurodegenerative disorder caused by loss of dopaminergic neurons in the substantia nigra. PD leads to dysfunction of the control of movements such as bradykinesia, akinesia, muscular rigidity, postural instability, and resting tremor. Several stuidies have suggested that causative genes for neurodegenerative diseases associated with lipid rafts. Also, PD-associated proteins, such as α-synuclein, LRRK2, parkin, and PINK1 associate with lipid rafts and lipid rafts may be associated with neurodegeneration. Previously, we observed that DJ-1, a causative gene for PD is palmitolylated and associates with lipid rafts ,which regulates the lipid raft-dependent endocytosis. Here, we observed whether DJ-1 regulates the expression of the lipid raft marker proteins. Especially, the expression of Caveolin-1 (Cav-1) and Flotillin-1 (Flot-1) was lower in astrocytes from DJ-1 KO mice than in those from WT mice. But the expression of other components, Cav-2 and Flot-2 was expressed in astrocytes from DJ-1 KO mice similar with those from WT mice. Also, DJ-1 interacted with Flot-1 but Cav-1. And overexpression of DJ-1 in DJ-1 KO cells increased the Cav-1 and Flot-1 and rescued the reduced endocytosis in DJ-1 KO cells. Furthermore, overexpression of Cav-1 and Flot-1 also rescued the lipid raft-dependent endocytosis in DJ-1 KO cells. This study suggests that DJ-1 regulates the expression of components of lipid rafts, Cav-1 and Flot-1, and involves in the lipid raft-dependent endocytosis, which might affect the pathogenesis of PD.
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