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- Title
Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest.
- Authors
Kyei, George B.; Vergne, Isabelle; Chua, Jennifer; Roberts, Esteban; Harris, James; Junutula, Jagath R.; Deretic, Vojo
- Abstract
Mycobacterium tuberculosis arrests phagosomal maturation in infected macrophage, and, apart from health significance, provides a superb model system to dissect the phagolysosomal biogenesis pathway. Here, we demonstrate a critical role for the small GTPase Rab14 in maintaining mycobacterial phagosome maturation block. Four-dimensional microscopy showed that phagosomes containing live mycobacteria accumulated Rab14 following phagocytosis. The recruitment of Rab14 had strong functional consequence, as a knockdown of endogenous Rab14 by siRNA or overexpression of Rab14 dominant-negative mutants (Rab14S25N and Rab14N125I) released the maturation block and allowed phagosomes harboring live mycobacteria to progress into phagolysosomes. Conversely, overexpression of the wild-type Rab14 and the constitutively active mutant Rab14Q70L prevented phagosomes with dead mycobacteria from undergoing default maturation into phagolysosomal organelles. Mechanistic studies demonstrated a role for Rab14 in stimulating organellar fusion between phagosomes and early endosomes but not with late endosomes. Rab14 enables mycobacterial phagosomes to maintain early endosomal characteristics and avoid late endosomal/lysosomal degradative components.
- Subjects
MYCOBACTERIUM tuberculosis; MACROPHAGES; GUANOSINE triphosphatase; ANTIGEN presenting cells; MICROSCOPY
- Publication
EMBO Journal, 2006, Vol 25, Issue 22, p5250
- ISSN
0261-4189
- Publication type
Article
- DOI
10.1038/sj.emboj.7601407