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The Potential Function Of SNX10 In Bacterial Infection

Posted on:2017-03-19Degree:DoctorType:Dissertation
Country:ChinaCandidate:J LouFull Text:PDF
GTID:1314330542466336Subject:Immunology
Abstract/Summary:
Sorting nexins(SNXs)are a large group of proteins that are localized in the cytoplasm and have the potential for membrane association either through their lipid-binding PX domain or through protein-protein interactions with membrane-associated protein complexes.Some members of this family have been shown to facilitate protein sorting.SNX10 is one of the simplest structured members in the SNX family and does not have other reported domain except the PX domain,thus specifically binding to PtdIns(3)P,which is a phospholipid found in endosomal membranes and important for exporting proteins that mediate endocytic,phagocytic and autophagic membrane traffic.SNX10 has been reported to induce giant vacuoles in mammalian cells and possess a regulatory function in endosomal morphology,which is crucial for the functions of macrophages,including phagocytosis and digestion of pathogens,inflammatory response,antigen processing and presentation.We suspected that SNX 10 might play an important role in innate immunity.In this article,we investigated its role in vivo and vitro by infecting Snx10-deficient mice with bacteria.We have discovered that the expression of SNX 10 in macrophages was upregulated after the stimulation of Listeria monocytogenes.Snx10-deficient mice are more susceptible to the infection of Listeria monocytogenes.The deficiency of SNX10 did not affect the production of cytokines or the activation of TLRs downward signaling pathway and it did not alleviate the uptake of Listeria monocytogenes or the production of ROS induced by LPS,while it exerted great influence on the killing of bacteria in macrophages.Further results revealed that SNX10 promoted the maturation of phagosomes by interacting with Monl-Cczl and HOPS complexes so as to affect the degradation process of bacteria inside the lysosomes.
Keywords/Search Tags:SNX10, Bacterial infections, Phagosome maturation
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