| First Author | Madan R | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 8 | Pages | 5574-87 |
| PubMed ID | 22190682 | Mgi Jnum | J:220506 |
| Mgi Id | MGI:5634883 | Doi | 10.1074/jbc.M111.286120 |
| Citation | Madan R, et al. (2012) Salmonella acquires lysosome-associated membrane protein 1 (LAMP1) on phagosomes from Golgi via SipC protein-mediated recruitment of host Syntaxin6. J Biol Chem 287(8):5574-87 |
| abstractText | Several intracellular pathogens have developed diverse strategies to avoid targeting to lysosomes. However, they universally recruit lysosome-associated membrane protein 1 (LAMP1); the mechanism of LAMP1 recruitment remains unclear. Here, we report that a Salmonella effector protein, SipC, specifically binds with host Syntaxin6 through its C terminus and thereby recruits Syntaxin6 and other accessory molecules like VAMP2, Rab6, and Rab8 on Salmonella-containing phagosomes (SCP) and acquires LAMP1 by fusing with LAMP1-containing Golgi-derived vesicles. In contrast, sipC knock-out:SCP (sipC(-):SCP) or sipC(M398K):SCP fails to obtain significant amounts of Syntaxin6 and is unable to acquire LAMP1. Moreover, phagosomes containing respective knock-out Salmonella like sipA(-), sipB(-), sipD(-), sopB(-), or sopE(-) recruit LAMP1, demonstrating the specificity of SipC in this process. In addition, depletion of Syntaxin6 by shRNA in macrophages significantly inhibits LAMP1 recruitment on SCP. Additionally, survival of sipC(-):Salmonella in mice is found to be significantly inhibited in comparison with WT:Salmonella. Our results reveal a novel mechanism showing how Salmonella acquires LAMP1 through a SipC-Syntaxin6-mediated interaction probably to stabilize their niche in macrophages and also suggest that similar modalities might be used by other intracellular pathogens to recruit LAMP1. |
