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

Cell Host & Microbe
Vitaly SedlyarovGiulio Superti-Furga

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.

Citations

Dec 24, 2018·Cellular Microbiology·Adriana Moldovan, Martin J Fraunholz
Sep 12, 2019·Physiological Reviews·S F Pedersen, L Counillon
Jan 27, 2019·Nature Reviews. Microbiology·Mike Tyers, Gerard D Wright
Sep 22, 2018·Cell Death and Differentiation·Astrid FausterGiulio Superti-Furga
Jul 20, 2019·Scientific Reports·Anna MoskovskichGiulio Superti-Furga
Jul 3, 2020·International Journal of Environmental Research and Public Health·Giuliano MolinariElsa Nervo
Oct 20, 2020·The Journal of Experimental Medicine·Jake R ThomasNaomi McGovern
Dec 3, 2020·Nature Communications·Enrico GirardiGiulio Superti-Furga
Jan 30, 2020·Acta Pharmaceutica Sinica. B·Wenxin SongLigong Chen
Feb 6, 2021·Frontiers in Immunology·Grace R PidwillSimon J Foster
Jan 29, 2021·Frontiers in Cell and Developmental Biology·Johannes Westman, Sergio Grinstein
Jan 11, 2021·Biochimica Et Biophysica Acta. Bioenergetics·Shane Austin, Karin Nowikovsky
Jan 6, 2021·Trends in Molecular Medicine·Christopher W Fell, Vanja Nagy
May 4, 2020·Current Opinion in Microbiology·Chunyi Zhou, Paul D Fey
Mar 6, 2021·Communications Biology·Christiane GasperiChris Cotsapas
Oct 3, 2020·Trends in Microbiology·Jeffrey S BourgeoisDennis C Ko
Jul 13, 2021·Frontiers in Cell and Developmental Biology·Markus RitterHubert H Kerschbaum
Aug 26, 2021·Cell Metabolism·Alissa TrzeciakJustin Shaun Arnold Perry
Aug 28, 2021·Frontiers in Pharmacology·Vojtech DvorakGiulio Superti-Furga
Sep 25, 2021·Antioxidants & Redox Signaling·Lincon Felipe Lima-SilvaPedro M Moraes-Vieira

❮ Previous
Next ❯

Methods Mentioned

BETA
flow cytometry
PMA
fluorescence-activated cell sorting
Knockout
FCS
transfection
PCR
RNA-Seq
scraping
Protein Assay

Software Mentioned

GenScript
QuikChange Primer Design
FlowJo X Star
DESeq2
R
Bioconductor
Rstudio IDE
Rstudio
Tasser Suite

Related Concepts

Related Feeds

CRISPR (general)

Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). CRISPR-Cas system enables the editing of genes to create or correct mutations. Discover the latest research on CRISPR here.

CRISPR for Genome Editing

Genome editing technologies enable the editing of genes to create or correct mutations. Clustered regularly interspaced short palindromic repeats (CRISPR) are DNA sequences in the genome that are recognized and cleaved by CRISPR-associated proteins (Cas). Here is the latest research on the use of CRISPR-Cas system in gene editing.