Ubiquitin trafficking to the lysosome: keeping the house tidy and getting rid of unwanted guests.
Bacterial killing by autophagic delivery to the lysosomal compartment has been shown for Mycobacteria, Streptococcus, Shigella, Legionella and Salmonella, indicating an important role for this conserved trafficking pathway for the control of intracellular bacterial pathogens.(1-5) In a recent study we found that solubilized lysosomes isolated from bone marrow-derived macrophages had potent antibacterial properties against M. tuberculosis and M. smegmatis that were associated with ubiquitin and ubiquitin-derived peptides. We propose that ubiquitinated proteins are delivered to the lysosomal compartment, where degradation by lysosomal proteinases generates ubiquitin-derived peptides with antimycobacterial properties. This surprising finding provokes a number of questions regarding the nature and trafficking of ubiquitin and ubiquitin-modified proteins in mammalian cells. We discuss the possible role(s) that the multivesicular body (MVB), the late endosome and the autophagosome may play in trafficking of ubiquitinated proteins to the lysosome.
Purdy
Georgiana E
GE
Department of Microbiology and Immunology, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA. gep9@cornell.edu
Russell
David G
DG
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001343:Autophagy / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D008247:Lysosomes / Q000502:physiology* / Q000648:ultrastructure; D008264:Macrophages / Q000382:microbiology / Q000648:ultrastructure; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000502:physiology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D022161:Transport Vesicles / Q000378:metabolism / Q000648:ultrastructure; D025801:Ubiquitin / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism* / Q000648:ultrastructure
D000900:Anti-Bacterial Agents; D010455:Peptides; D025801:Ubiquitin