Wei Yonghang, Awan Maher Un Nisa, Bai Liping, Bai Jie
Laboratory of Molecular Neurobiology, Medical School, Kunming University of Science and Technology, Kunming, China.
Front Mol Neurosci. 2023 Feb 21;16:1097633. doi: 10.3389/fnmol.2023.1097633. eCollection 2023.
Parkinson's disease (PD) is a chronic neurodegenerative disease associated with the intracellular organelles. Leucine-rich repeat kinase 2 (LRRK2) is a large multi-structural domain protein, and mutation in LRRK2 is associated with PD. LRRK2 regulates intracellular vesicle transport and function of organelles, including Golgi and lysosome. LRRK2 phosphorylates a group of Rab GTPases, including Rab29, Rab8, and Rab10. Rab29 acts in a common pathway with LRRK2. Rab29 has been shown to recruit LRRK2 to the Golgi complex (GC) to stimulate LRRK2 activity and alter the Golgi apparatus (GA). Interaction between LRRK2 and Vacuolar protein sorting protein 52 (VPS52), a subunit of the Golgi-associated retrograde protein (GARP) complex, mediates the function of intracellular soma trans-Golgi network (TGN) transport. VPS52 also interacts with Rab29. Knockdown of VPS52 leads to the loss of LRRK2/Rab29 transported to the TGN. Rab29, LRRK2, and VPS52 work together to regulate functions of the GA, which is associated with PD. We highlight recent advances in the roles of LRRK2, Rabs, VPS52, and other molecules, such as Cyclin-dependent kinase 5 (CDK5) and protein kinase C (PKC) in the GA, and discuss their possible association with the pathological mechanisms of PD.
帕金森病（PD）是一种与细胞内细胞器相关的慢性神经退行性疾病。富含亮氨酸重复激酶2（LRRK2）是一种具有多个结构域的大型蛋白质，LRRK2突变与帕金森病相关。LRRK2调节细胞内囊泡运输和细胞器功能，包括高尔基体和溶酶体。LRRK2使一组Rab GTP酶磷酸化，包括Rab29、Rab8和Rab10。Rab29与LRRK2在共同途径中发挥作用。已证明Rab29将LRRK2招募至高尔基体复合体（GC）以刺激LRRK2活性并改变高尔基体（GA）。LRRK2与液泡蛋白分选蛋白52（VPS52）相互作用，VPS52是高尔基体相关逆行蛋白（GARP）复合体的一个亚基，介导细胞内胞体反式高尔基体网络（TGN）运输的功能。VPS也与Rab29相互作用。敲低VPS52会导致转运至TGN的LRRK2/Rab29丢失。Rab29、LRRK2和VPS52共同作用调节与帕金森病相关的高尔基体功能。我们重点介绍了LRRK2、Rab蛋白、VPS52以及其他分子，如细胞周期蛋白依赖性激酶5（CDK5）和蛋白激酶C（PKC）在高尔基体中的作用的最新进展，并讨论了它们与帕金森病病理机制的可能关联。
