Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305-5307, U.S.A.
Biochem Soc Trans. 2018 Dec 17;46(6):1707-1712. doi: 10.1042/BST20180470. Epub 2018 Nov 22.
Leucine-rich repeat kinase 2 (LRRK2) is mutated in familial Parkinson's disease, and pathogenic mutations activate the kinase activity. A tour de force screen by Mann and Alessi and co-workers identified a subset of Rab GTPases as bona fide LRRK2 substrates. Rab GTPases are master regulators of membrane trafficking and this short review will summarize what we know about the connection between LRRK2 and this family of regulatory proteins. While, in most cases, Rab GTPase phosphorylation is predicted to interfere with Rab protein function, the discovery of proteins that show preferential binding to phosphorylated Rabs suggests that more complex interactions may also contribute to mutant LRRK2-mediated pathology.
富含亮氨酸重复激酶 2（LRRK2）在家族性帕金森病中发生突变，并且致病性突变会激活激酶活性。Mann 和 Alessi 及其同事的一项杰出筛选发现，一小部分 Rab GTPases 是 LRRK2 的真正底物。Rab GTPases 是膜运输的主要调节剂，这篇简短的综述将总结我们对 LRRK2 与这一家族调节蛋白之间联系的了解。虽然在大多数情况下，Rab GTPase 磷酸化预计会干扰 Rab 蛋白的功能，但发现优先与磷酸化 Rab 结合的蛋白质表明，更复杂的相互作用也可能导致突变 LRRK2 介导的病理学。
