The ERM protein, ezrin, regulates neutrophil transmigration by modulating the apical localization of MRP2 in response to the SipA effector protein during Salmonella Typhimurium infection.

Publisher: Hindawi Country of Publication: India NLM ID: 100883691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1462-5822 (Electronic) Linking ISSN: 14625814 NLM ISO Abbreviation: Cell Microbiol Subsets: MEDLINE

Publication: 2022- : Mumbai : Hindawi
Original Publication: Oxford : Wiley-Blackwell, c1999-

Cell Movement*; Bacterial Proteins/*metabolism ; Cytoskeletal Proteins/*metabolism ; Microfilament Proteins/*metabolism ; Multidrug Resistance-Associated Proteins/*metabolism ; Neutrophils/*metabolism ; Salmonella Infections/*metabolism ; Salmonella typhimurium/*pathogenicity; Bacterial Proteins/genetics ; Benzophenanthridines/pharmacology ; Blotting, Western ; Carbazoles/pharmacology ; Cell Line, Tumor ; Cytoskeletal Proteins/genetics ; Humans ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/microbiology ; Microfilament Proteins/genetics ; Multidrug Resistance-Associated Protein 2 ; Multidrug Resistance-Associated Proteins/genetics ; Phosphorylation ; Protein Kinase C-alpha/genetics ; Protein Kinase C-alpha/metabolism ; Protein Transport ; RNA, Small Interfering/genetics ; RNA, Small Interfering/metabolism ; Salmonella Infections/microbiology ; Salmonella typhimurium/drug effects ; Salmonella typhimurium/genetics ; Salmonella typhimurium/metabolism ; Transfection

In human disease induced by Salmonella enterica serovar Typhimurium (S. Typhimurium), transepithelial migration of neutrophils rapidly follows attachment of the bacteria to the epithelial apical membrane. We have previously shown that during S. Typhimurium infection the multidrug resistance-associated protein 2 (MRP2) is highly expressed at the apical surface of the intestinal epithelia, and that it functions as an efflux pump for the potent neutrophil chemoattractant hepoxilin A(3) . However, the molecular mechanisms regulating its apical localization during active states of inflammation remain unknown. Thus, our objective was to determine the mechanistic basis for the translocation of MRP2 to the apical surface of intestinal epithelial cells during S. Typhimurium infection. We show that suppression of ezrin, through either RNAi or truncation of the C-terminus, results not only in a decrease in S. Typhimurium-induced neutrophil transmigration but also significantly attenuates the apical membrane expression of MRP2 during Salmonella infection. In addition, we determined that S. Typhimurium induces the activation of ezrin via a PKC-α-dependent pathway and that ezrin activation is coupled to apical localization of MRP2. Based on these results we propose that activation of ezrin is required for the apical localization of MRP2 during S. Typhimurium infection.
(© 2011 Blackwell Publishing Ltd.)

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R01 DK056754 United States DK NIDDK NIH HHS; R01 DK056754-12 United States DK NIDDK NIH HHS; R01 DK056754-13 United States DK NIDDK NIH HHS; DK56754 United States DK NIDDK NIH HHS

0 (ABCC2 protein, human)
0 (Bacterial Proteins)
0 (Benzophenanthridines)
0 (Carbazoles)
0 (Cytoskeletal Proteins)
0 (Microfilament Proteins)
0 (Multidrug Resistance-Associated Protein 2)
0 (Multidrug Resistance-Associated Proteins)
0 (RNA, Small Interfering)
0 (SipA protein, Salmonella)
0 (ezrin)
136194-77-9 (Go 6976)
E3B045W6X0 (chelerythrine)
EC 2.7.11.13 (Protein Kinase C-alpha)

Date Created: 20110909 Date Completed: 20120227 Latest Revision: 20211203

20231215

PMC3218228

10.1111/j.1462-5822.2011.01693.x

21899702