UM
NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation
Cai,Cui Zan1; Yang,Chuanbin2; Zhuang,Xu Xu1; Yuan,Ning Ning1; Wu,Ming Yue1; Tan,Jie Qiong3; Song,Ju Xian2,4; Cheung,King Ho2; Su,Huanxing1; Wang,Yi Tao1; Tang,Bei Sha5; Behrends,Christian6; Durairajan,Siva Sundara Kumar2,7; Yue,Zhenyu8; Li,Min2; Lu,Jia Hong1
2020
Source PublicationAutophagy
ISSN1554-8627
AbstractNRBF2 is a component of the class III phosphatidylinositol 3-kinase (PtdIns3K) complex. Our previous study has revealed its role in regulating ATG14-associated PtdIns3K activity for autophagosome initiation. In this study, we revealed an unknown mechanism by which NRBF2 modulates autophagosome maturation and APP-C-terminal fragment (CTF) degradation. Our data showed that NRBF2 localized at autolysosomes, and loss of NRBF2 impaired autophagosome maturation. Mechanistically, NRBF2 colocalizes with RAB7 and is required for generation of GTP-bound RAB7 by interacting with RAB7 GEF CCZ1-MON1A and maintaining the GEF activity. Specifically, NRBF2 regulates CCZ1-MON1A interaction with PI3KC3/VPS34 and CCZ1-associated PI3KC3 kinase activity, which are required for CCZ1-MON1A GEF activity. Finally, we showed that NRBF2 is involved in APP-CTF degradation and amyloid beta peptide production by maintaining the interaction between APP and the CCZ1-MON1A-RAB7 module to facilitate the maturation of APP-containing vesicles. Overall, our study revealed a pivotal role of NRBF2 as a new RAB7 effector in modulating autophagosome maturation, providing insight into the molecular mechanism of NRBF2-PtdIns3K in regulating RAB7 activity for macroautophagy/autophagy maturation and Alzheimer disease-associated protein degradation.
KeywordAmaturation Autophagy CCZ1-MON1A NRBF2 PI3KC3/VPS34 RAB7 trafficking
DOI10.1080/15548627.2020.1760623
URLView the original
Language英语
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Cited Times [WOS]:2   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Affiliation1.Institute of Chinese Medical Sciences,University of Macau,State Key Laboratory of Quality Research in Chinese Medicine,Macao
2.Hong Kong Baptist University,Centre for Parkinson’s Disease Research,School of Chinese Medicine,Hong Kong
3.School of Life Sciences,Central South University,Center for Medical Genetics,Changsha,China
4.Guangzhou University of Chinese Medicine,Medical College of Acupuncture-Moxibustion and Rehabilitation,Guangzhou,China
5.Xiangya Hospital,Central South University,Department of Neurology,Changsha,China
6.Ludwig-Maximilians-Universität München,Munich Cluster for Systems Neurology (Synergy),München,Germany
7.School of Life Sciences,Central University of Tamil Nadu,Division of Mycobiology and Neurodegenerative Disease Research,Department of Microbiology,Tiruvarur,India
8.Friedman Brain Institute,Icahn School of Medicine at Mount Sinai,Department of Neurology and Neuroscience,New York,United States
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Cai,Cui Zan,Yang,Chuanbin,Zhuang,Xu Xu,et al. NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation[J]. Autophagy,2020.
APA Cai,Cui Zan.,Yang,Chuanbin.,Zhuang,Xu Xu.,Yuan,Ning Ning.,Wu,Ming Yue.,...&Lu,Jia Hong.(2020).NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation.Autophagy.
MLA Cai,Cui Zan,et al."NRBF2 is a RAB7 effector required for autophagosome maturation and mediates the association of APP-CTFs with active form of RAB7 for degradation".Autophagy (2020).
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