Mycobacterium bovisBCG disrupts the interaction of Rab7 with RILP contributing to inhibition of phagosome maturation

Autor: Hafid Soualhine, Jim Sun, Cecilia Bucci, Thomas Hong, Zakaria Hmama, Ala-Eddine Deghmane, Anna Solodkin
Přispěvatelé: University of British Columbia (UBC), Vancouver Coastal Health Research Institute (VCH), Università del Salento [Lecce], This work was supported by operating grants from the Canadian Institutes of Health Research (CIHR) MOP-67232/-84557 and BC Lung Association. Z.H. was supported by scholar awards from MSFHR and the CIHR. J.S. and H.S. were supported by the TBVets Charitable Foundation. A.D. is the recipient of a MSFHR and a CIHR postdoctoral fellowship., Sun, J, DEGHMANE A., E, Soualhine, H, Hong, T, Bucci, Cecilia, Solodkin, A, Hmama, Z.
Rok vydání: 2007
Předmět:
MESH: Mycobacterium bovis
GTP'
confocal microscopy
Diffusion
Mice
0302 clinical medicine
Phagosomes
Rab7
Immunology and Allergy
Macrophage
MESH: Animals
MESH: Microbial Viability
Phagosome
0303 health sciences
030302 biochemistry & molecular biology
MESH: Diffusion
phagocytosi
phagosome
Mycobacterium bovis
3. Good health
Cell biology
Vesicular transport protein
Protein Binding
Endosome
GTPase activating protein
Immunology
MESH: Carrier Proteins
Biology
Microbiology
03 medical and health sciences
lysosomes
MESH: Phagosomes
MESH: Mice
Inbred C57BL
Mycobacterium bovi
Phagosome maturation
Animals
MESH: Protein Binding
GTPase
MESH: Mice
030304 developmental biology
Host-pathogen interaction
Microbial Viability
Macrophages
rab7 GTP-Binding Proteins
MESH: Macrophages
Lipid bilayer fusion
Cell Biology
[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology
latex beads
Mice
Inbred C57BL
MESH: rab GTP-Binding Proteins
rab GTP-Binding Proteins
Rab
Carrier Proteins
RILP
030217 neurology & neurosurgery
Zdroj: Journal of Leukocyte Biology
Journal of Leukocyte Biology, Society for Leukocyte Biology, 2007, 82 (6), pp.1437-1445. ⟨10.1189/jlb.0507289⟩
ISSN: 1938-3673
0741-5400
Popis: Phagosomes containing M. tuberculosis and M. bovis BCG interact normally with early endosomes but fail to fuse with late endosomes and lysosomes. Whereas many early events of myco- bacterial phagosomes have been elucidated, the exact mechanism of the inhibition of fusion with lysosomes is still unclear. Several Rab GTPase proteins were shown to be involved in membrane fusion and vesicular transport. In particular, Rab7 associates with the phagosomal membrane and regulates the fusion between late endosomes and lysosomes. This function of Rab7 was shown to be mediated in epithelial cell models by the Rab7 effector RILP (Rab7-interacting lysosomal protein). However, the relevance of Rab7-RILP interaction to phagosome biogenesis in macro- phage infected with mycobacteria is still un- known. In this study, cotransfection of RAW 264.7 cells with Rab7 and RILP revealed that Rab7-RILP interaction occurs in macrophages ingesting latex beads. Thereafter, this cell system model was used to demonstrate that infection with live but not killed M. bovis BCG inhibited RILP recruitment despite Rab7 acquisition by the phagosome. Further investigation using im- mobilized RILP to pull down active Rab7 (GTP- bound form) from macrophage lysates demon- strated that inactive Rab7 (GDP-bound form) predominates in cells infected with live BCG. In addition, cell-free system experiments demon- strated that BCG culture supernatant contains a factor that catalyzes the GTP/GDP switch on recombinant Rab7 molecules. Such a factor was shown to diffuse beyond BCG phagosomes and target other Rab7-positive compartments. These findings suggest that live mycobacteria express within the macrophage a Rab7 deactivating fac- tor leading to abortion of RILP-mediated fusion with lysosomes. J. Leukoc. Biol. 82: 000-000; 2007.
Databáze: OpenAIRE
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