Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
Unbiased screen for interactors of leucine-rich repeat kinase 2 supports a common pathway for sporadic and familial Parkinson disease
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DOI：
10.1073/pnas.1318306111
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发表时间：
2014-02-18
影响因子：
11.1
通讯作者：
Cookson, Mark R.
中科院分区：
文献类型：
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作者：
Beilina, Alexandria;Rudenko, Iakov N.;Cookson, Mark R.
富含亮氨酸重复序列激酶2（LRRK 2）的突变导致遗传性帕金森病（PD），LRRK 2周围的常见变异是散发性PD的风险因素。使用蛋白质-蛋白质相互作用阵列，我们确定BCL 2相关的athanogene 5，Rab 7 L1（RAB 7，成员RAS癌基因家族样1），和细胞周期蛋白G相关激酶作为LRRK 2的结合伴侣。后两个基因是通过全基因组关联研究确定的散发性PD风险的候选基因。这些蛋白质形成复合物，其促进高尔基体衍生的囊泡通过体外和体内的自噬-溶酶体系统的清除。我们认为三种不同的PD基因具有共同的生物学功能。更一般地说，来自多个无偏筛选的数据整合可以提供对人类疾病机制的洞察。
Mutations in leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson disease (PD), and common variants around LRRK2 are a risk factor for sporadic PD. Using protein-protein interaction arrays, we identified BCL2-associated athanogene 5, Rab7L1 (RAB7, member RAS oncogene family-like 1), and Cyclin-G-associated kinase as binding partners of LRRK2. The latter two genes are candidate genes for risk for sporadic PD identified by genome-wide association studies. These proteins form a complex that promotes clearance of Golgi-derived vesicles through the autophagy-lysosome system both in vitro and in vivo. We propose that three different genes for PD have a common biological function. More generally, data integration from multiple unbiased screens can provide insight into human disease mechanisms.