Bacteria-generated PtdIns(3)P recruits VAMP8 to facilitate phagocytosis.
Salmonella enterica serovar Typhimurium invades non-phagocytic cells by inducing macropinocytosis. SopB is involved in modulating actin dynamics to promote Salmonella-induced invasion. We report here that SopB-generated PtdIns(3)P binds VAMP8/endobrevin to promote efficient bacterial phagocytosis. VAMP8 is recruited to Salmonella-induced macropinosomes in a nocodazole-dependent, but Brefeldin A-independent, manner. We found that VAMP8 directly binds to and colocalizes with PtdIns(3)P. The inositol phosphatase activity of SopB is required for PtdIns(3)P and VAMP8 accumulation, while wortmannin, a specific phosphatidylinositol 3-kinase inhibitor, has no effect. Knockdown of endogenous VAMP8 by small interfering RNA or expression of a truncated VAMP8 (1-79aa) reduces the invasion level of wild-type Salmonella to that of the phosphatase-deficient SopB(C460S) mutant. Our study demonstrates that Salmonella exploit host SNARE proteins and vesicle trafficking to promote bacterial entry.
Dai
Shipan
S
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Zhang
Ying
Y
Weimbs
Thomas
T
Yaffe
Michael B
MB
Zhou
Daoguo
D
D001426:Bacterial Proteins / Q000502:physiology; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D010586:Phagocytes / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology*; D018129:Phosphatidylinositol Phosphates / Q000096:biosynthesis* / Q000502:physiology; D050683:R-SNARE Proteins / Q000378:metabolism* / Q000502:physiology; D012486:Salmonella typhimurium / Q000472:pathogenicity / Q000502:physiology*
D001426:Bacterial Proteins; D018129:Phosphatidylinositol Phosphates; D050683:R-SNARE Proteins; C112938:VAMP8 protein, human; C055525:phosphatidylinositol 3-phosphate; C489224:SopB protein, Salmonella