Autophagy regulation revealed by SapM-induced block of autophagosome-lysosome fusion via binding RAB7

The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an importa...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2015-05, Vol.461 (2), p.401-407
Main Authors: Hu, Dong, Wu, Jing, Wang, Wan, Mu, Min, Zhao, Runpeng, Xu, Xuewei, Chen, Zhaoquan, Xiao, Jian, Hu, Fengyu, Yang, Yabo, Zhang, Rongbo
Format: Article
Language:English
Subjects:
60 APPLIED LIFE SCIENCES
Animals
Autophagy
Cell Line
COMPUTERIZED TOMOGRAPHY
DRUGS
Fusion
Host-Pathogen Interactions
LIPOPROTEINS
Lysosome
Lysosomes - metabolism
Lysosomes - microbiology
MACROPHAGES
Membrane Fusion
Mice
MYCOBACTERIUM TUBERCULOSIS
Mycobacterium tuberculosis - enzymology
Mycobacterium tuberculosis - physiology
Phagosomes - metabolism
Phagosomes - microbiology
Phosphoric Monoester Hydrolases - metabolism
rab GTP-Binding Proteins - metabolism
Rab7
SapM
TUBERCULOSIS
Tuberculosis - enzymology
Tuberculosis - metabolism
Tuberculosis - microbiology
VACCINES
VIRULENCE
Virulence Factors - metabolism
VISIBLE RADIATION
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Summary:The mechanism underlying autophagy alteration by mycobacterium tuberculosis remains unclear. Our previous study shows LpqH, a lipoprotein of mycobacterium tuberculosis, can cause autophagosomes accumulation in murine macrophages. It is well known that SapM, another virulence factor, plays an important role in blocking phagosome-endosome fusion. However, the mechanism that SapM interferes with autophagy remains poorly defined. In this study, we report that SapM suppresses the autophagy flux by blocking autophagosome fusion with lysosome. Exposure to SapM results in accumulations of autophagosomes and decreased co-localization of autophagosome with lysosome. Molecularly, Rab7, a small GTPase, is blocked by SapM through its CT domain and is prevented from involvement of autophagosome-lysosome fusion. In conclusion, our study reveals that SapM takes Rab7 as a previously unknown target to govern a distinct molecular mechanism underlying autophagosome-lysosome fusion, which may bring light to a new thought about developing potential drugs or vaccines against tuberculosis. •A mechanism for disrupting autophagosome-lysosome fusion induced by SapM.•Rab7 is involved in SapM-inhibited autophagy.•SapM interacts with Rab7 by CT-domain.•CT-domain is indispensable to SapM-inhibited autophagy.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2015.04.051