Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection

	Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection
	Qi XP 1; Man SM 1; Gurung P 1; Neale G 2; Guy CG 1; Lamkanfi M 3,4; Kanneganti T-D[*]1; Malireddi RKS 1; Karki R 1; Lupfer C 1
刊名	JOURNAL OF EXPERIMENTAL MEDICINE
	2016
卷号	213 期号:10 页码:2081–2097
通讯作者	thirumala-devi.kanneganti@stjude. org
英文摘要	Lysosomal cathepsins regulate an exquisite range of biological functions, and their deregulation is associated with inflammatory, metabolic, and degenerative diseases in humans. In this study, we identified a key cell-intrinsic role for cathepsin B as a negative feedback regulator of lysosomal biogenesis and autophagy. Mice and macrophages lacking cathepsin B activity had increased resistance to the cytosolic bacterial pathogen Francisella novicida. Genetic deletion or pharmacological inhibition of cathepsin B down-regulated mechanistic target of rapamycin activity and prevented cleavage of the lysosomal calcium channel TRP ML1. These events drove transcription of lysosomal and autophagy genes via transcription factor EB, which increased lysosomal biogenesis and activation of autophagy initiation kinase ULK1 for clearance of the bacteria. Our results identified a fundamental biological function of cathepsin B in providing a checkpoint for homeostatic maintenance of lysosome populations and basic recycling functions in the cell.
收录类别	SCI
资助信息	This work was supported by the US National Institutes of Health (AI101935, AI124346, AR056296, and CA163507 to T.-D. Kanneganti), the American Lebanese Syrian Associated Charities (grant to T.-D. Kanneganti), the European Research Coun- cil (281600 to M. Lamkanfi), the Fund for Scientific Research-Flanders (G030212N to M. Lamkanfi), and the National Health and Medical Research Council of Australia (R.G. Menzies Early Career Fellowship APP1091544 to S.M. Man).
语种	英语
内容类型	期刊论文
源URL	[http://159.226.149.26:8080/handle/152453/11269]
专题	昆明动物研究所_科研共享资源
作者单位	1.Department of Immunology,St. Jude Children's Research Hospital, Memphis, TN 38105 2.Hartwell Center for Bioinformatics and Biotechnology,St. Jude Children's Research Hospital, Memphis, TN 38105 3.Inflammation Research Center, VIB, B-9052 Zwijnaarde-Ghent, Belgium 4.Department of Internal Medicine, Ghent University, B-9000 Ghent, Belgium
推荐引用方式 GB/T 7714	Qi XP,Man SM,Gurung P,et al. Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection[J]. JOURNAL OF EXPERIMENTAL MEDICINE,2016,213(10):2081–2097.
APA	Qi XP.,Man SM.,Gurung P.,Neale G.,Guy CG.,...&Lupfer C.(2016).Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection.JOURNAL OF EXPERIMENTAL MEDICINE,213(10),2081–2097.
MLA	Qi XP,et al."Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection".JOURNAL OF EXPERIMENTAL MEDICINE 213.10(2016):2081–2097.