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

• Published in: Biochemical and biophysical research communications Vol. 461; no. 2; pp. 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: Journal Article
• Language: English
• Published: United States Elsevier Inc 29.05.2015
• 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; Rab7; Tuberculosis; SapM; Autophagy; Fusion; Lysosome
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2015.04.051

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.