The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification.

Details

Serval ID
serval:BIB_2F9360B2E685
Type
Article: article from journal or magazin.
Collection
Publications
Title
The Bicarbonate Transporter SLC4A7 Plays a Key Role in Macrophage Phagosome Acidification.
Journal
Cell host & microbe
Author(s)
Sedlyarov V., Eichner R., Girardi E., Essletzbichler P., Goldmann U., Nunes-Hasler P., Srndic I., Moskovskich A., Heinz L.X., Kartnig F., Bigenzahn J.W., Rebsamen M., Kovarik P., Demaurex N., Superti-Furga G.
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Publication state
Published
Issued date
13/06/2018
Peer-reviewed
Oui
Volume
23
Number
6
Pages
766-774.e5
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Macrophages represent the first line of immune defense against pathogens, and phagosome acidification is a necessary step in pathogen clearance. Here, we identified the bicarbonate transporter SLC4A7, which is strongly induced upon macrophage differentiation, as critical for phagosome acidification. Loss of SLC4A7 reduced acidification of phagocytosed beads or bacteria and impaired the intracellular microbicidal capacity in human macrophage cell lines. The phenotype was rescued by wild-type SLC4A7, but not by SLC4A7 mutants, affecting transport capacity or cell surface localization. Loss of SLC4A7 resulted in increased cytoplasmic acidification during phagocytosis, suggesting that SLC4A7-mediated, bicarbonate-driven maintenance of cytoplasmic pH is necessary for phagosome acidification. Altogether, we identify SLC4A7 and bicarbonate-driven cytoplasmic pH homeostasis as an important element of phagocytosis and the associated microbicidal functions in macrophages.
Keywords
Bicarbonates/metabolism, CRISPR-Cas Systems, Cation Transport Proteins/metabolism, Cytoplasm/metabolism, Gene Knockout Techniques, Homeostasis, Humans, Hydrogen-Ion Concentration, Macrophages/metabolism, Phagocytosis, Phagosomes/metabolism, Sodium-Bicarbonate Symporters/genetics, Sodium-Bicarbonate Symporters/physiology, THP-1 Cells, Transcriptome, U937 Cells, CRISPR screen, NBC3, NBCn1, SLC4A7, intracellular bacterial killing, macrophages, phagocytosis, phagosome acidification, solute carrier
Pubmed
Web of science
Open Access
Yes
Create date
11/08/2020 16:06
Last modification date
13/08/2020 5:26
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