The Salmonella effector PipB2 affects late endosome/lysosome distribution to mediate Sif extension.
After internalization into mammalian cells, the bacterial pathogen Salmonella enterica resides within a membrane-bound compartment, the Salmonella-containing vacuole (SCV). During its maturation process, the SCV interacts extensively with host cell endocytic compartments, especially late endosomes/lysosomes (LE/Lys) at later stages. These interactions are mediated by the activities of multiple bacterial and host cell proteins. Here, we show that the Salmonella type III effector PipB2 reorganizes LE/Lys compartments in mammalian cells. This activity results in the centrifugal extension of lysosomal glycoprotein-rich membrane tubules, known as Salmonella-induced filaments, away from the SCV along microtubules. Salmonella overexpressing pipB2 induce the peripheral accumulation of LE/Lys compartments, reducing the frequency of LE/Lys tubulation. Furthermore, ectopic expression of pipB2 redistributes LE/Lys, but not other cellular organelles, to the cell periphery. In coexpression studies, PipB2 can overcome the effects of dominant-active Rab7 or Rab34 on LE/Lys positioning. Deletion of a C-terminal pentapeptide motif of PipB2, LFNEF, prevents its peripheral targeting and effect on organelle positioning. The PipB2 homologue PipB does not possess this motif or the same biological activity as PipB2. Therefore, it seems that a divergence in the biological functions of these two effectors can be accounted for by sequence divergence in their C termini.
Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840, USA. lknodler@niaid.nih.gov
Leigh A
LA
Knodler
Olivia
O
Steele-Mortimer
D020816:Amino Acid Motifs / Q000235:genetics; D001426:Bacterial Proteins / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D008870:Microtubules / Q000382:microbiology / Q000502:physiology; D017434:Protein Structure, Tertiary; D012486:Salmonella typhimurium / Q000502:physiology*
D001426:Bacterial Proteins; C478164:PipB protein, Salmonella enterica; C478165:PipB2 protein, Salmonella enterica