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  • The EMBO Journal (2006) 25, 5250 - 5259
  • doi:10.1038/sj.emboj.7601407

Published online: 2 November 2006

Rab14 is critical for maintenance of Mycobacterium tuberculosis phagosome maturation arrest

George B Kyei1, Isabelle Vergne1, Jennifer Chua1, Esteban Roberts1, James Harris1, Jagath R Junutula2 and Vojo Deretic1,3

  1. Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM, USA
  2. Genentech Inc., South San Francisco, CA, USA
  3. Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, USA

Correspondence to:

Vojo Deretic, Departments of Molecular Genetics & Microbiology, and Cell Biology and Physiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE, Albuquerque, NM 87131-001, USA. Tel.: +1 505 272 0291; Fax: +1 505 272 5309; E-mail: vderetic@salud.unm.edu

Received 13 March 2006; Accepted 5 October 2006

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.

  • Keywords:

    • endosome,
    • lysosome,
    • phagosome,
    • Rab,
    • tuberculosis