DJ-1 associates with membrane trafficking system.

帕金森病(PD)是一种由多巴胺能神经元丢失引起的神经退行性疾病。尽管许多报道表明遗传因素与帕金森病的发病有关，但选择性多巴胺能神经元变性的分子机制仍不清楚。DJ-1是Park7连锁的常染色体隐性遗传型早发性帕金森病的致病基因。在这个项目中，我和我的同事揭示了DJ-1在培养细胞和从小鼠脑获得的原代神经元中以点状分布在胞浆和膜结构中。此外，DJ-1与GM130、突触素和Rab3A共定位。Forster共振能量转移分析显示，在活细胞中，一小部分DJ-1与突触素相互作用。虽然野生型DJ-1蛋白不需要中间蛋白而直接与膜结合，但致病性DJ-1的L166P突变与突触小泡的结合较少。这些结果表明，DJ-1与包括突触膜在内的膜细胞器结合，发挥其正常的功能。

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. In this project, my colleagues and I revealed 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. Additionally, DJ-1 colocalizes with GM130, synaptophysin and Rab3A. Forster 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.