Interconversions of phosphoinositides play a pivotal role during phagocytosis and at the subsequent stages of phagosomal maturation into the phagolysosome. Several model systems have been used to study the role of phosphoinositides in phagosomal membrane remodelling. These include phagosomes formed by inanimate objects such as latex beads, or pathogenic bacteria, e.g. Mycobacterium tuberculosis. The latter category provides naturally occurring tools to dissect membrane trafficking processes governing phagolysosome biogenesis. M. tuberculosis persists in infected macrophages by blocking Rab conversion and affecting Rab effectors. One of the major Rab effectors involved in this process is the type III phosphatidylinositol 3-kinase hVPS34. The lipid kinase hVPS34 and its enzymatic product PtdIns3P are critical for the default pathway of phagosomal maturation into phagolysosomes. Mycobacteria block PtdIns3P production and thus arrest phagosomal maturation. PtdIns3P is also critical for the process of autophagy, recently recognized as an effector of innate immunity defenses. Induction of autophagy by pharmacological, physiological, or immunological means, overcomes mycobacterial phagosome maturation block in a PtdIns3P generation dependent manner and eliminates intracellular M. tuberculosis. PtdIns3P and PtdIns3P-dependent processes represent an important cellular nexus where fundamental trafficking processes, disease causing host–pathogen interactions, and innate and adaptive immunity defense mechanisms meet.
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January 2007
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January 21 2007
Phosphoinositides in phagolysosome and autophagosome biogenesis
Vojo Deretic;
Vojo Deretic
1
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
†Cell Biology and Physiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
1To whom correspondence should be addressed (email [email protected]).
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Sudha Singh;
Sudha Singh
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Sharon Master;
Sharon Master
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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George Kyei;
George Kyei
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Alex Davis;
Alex Davis
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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John Naylor;
John Naylor
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Sergio de Haro;
Sergio de Haro
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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James Harris;
James Harris
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Monica Delgado;
Monica Delgado
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Esteban Roberts;
Esteban Roberts
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Isabelle Vergne
Isabelle Vergne
*Departments of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud, NE Albuquerque, NM 87131-001, U.S.A.
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Publisher: Portland Press Ltd
Online ISSN: 1744-1439
Print ISSN: 0067-8694
© 2006 Biochemical Society
2006
Biochem Soc Symp (2007) 74: 141–148.
Citation
Michael J.O. Wakelam, Vojo Deretic, Sudha Singh, Sharon Master, George Kyei, Alex Davis, John Naylor, Sergio de Haro, James Harris, Monica Delgado, Esteban Roberts, Isabelle Vergne; Phosphoinositides in phagolysosome and autophagosome biogenesis. Biochem Soc Symp 12 January 2007; 74 141–148. doi: https://doi.org/10.1042/BSS2007c13
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