期刊
CURRENT OPINION IN CELL BIOLOGY
卷 63, 期 -, 页码 102-113出版社
CURRENT BIOLOGY LTD
DOI: 10.1016/j.ceb.2020.01.001
关键词
Rab GTPase; RILPL1; Signal transduction; Protein kinase; Ciliogenesis; Lysosomal stress; Neuroinflammation
类别
资金
- Michael J. Fox Foundation for Parkinson's Research [17298, 6986]
- UK Medical Research Council [MC_UU_12016/2]
- Boehringer-Ingelheim, Germany
- Merck KGaA
- UK Medical Research Council
- GlaxoSmithKline
- MRC [MC_UU_12016/2, MR/P00704X/1, G0700656, MC_UU_00018/1] Funding Source: UKRI
Autosomal dominant missense mutations that hyperactivate the leucine-rich repeat protein kinase-2 (LRRK2) are a common cause of inherited Parkinson's disease and therapeutic efficacy of LRRK2 inhibitors is being tested in clinical trials. In this review, we discuss the nuts and bolts of our current understanding of how the LRRK2 is misregulated by mutations and how pathway activity is affected by LRRK2 binding to membrane, microtubule filaments, and 14-3-3, as well as by upstream components such as Rab29 and VPS35. We discuss recent work that points toward a subset of Rab proteins comprising key physiological substrates that bind new sets of effectors, such as RILPL1/2, JIP3 and JIP4 after phosphorylation by LRRK2. We explore what is known about how LRRK2 regulates ciliogenesis, the endosomal-lysosomal system, immune responses and interplay with alpha-synuclein and tau and how this might be linked to Parkinson's' disease.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据