ASAP1 regulates the uptake of Mycobacterium tuberculosis H37Ra in THP1-derived macrophages by remodeling actin cytoskeleton. (July 2021)

• Record Type: Journal Article
• Authors: Cui, Jia; Chen, Guangxin; Zhao, Zhonghua; Wang, Liqing; Wen, Da; Xing, Li; Wu, Changxin
• Is Part Of: Tuberculosis. Volume 129(2021)
• Publication Date: 2021-07
• Subjects: ASAP1 -- Mycobacterium -- THP-1 -- Actin cytoskeleton -- H37Ra; ACAPs Arf-GAP with coiled-coil -- ANK repeat and PH domain-containing proteins -- ADAP1 ArfGAP With Dual PH Domains 1 -- AGAPs ArfGAP with GTPase Domain -- ANK Repeat and PH domain-containing proteins -- ARAPs ArfGAP with RhoGAP domain -- Arf-GAPs ADP ribosylation factor (Arf)-GTPase activating proteins -- Arf ADP ribosylation factor -- ASAPs ArfGAP with SH3 domain -- CDRs circular dorsal ruffles -- DCs dendritic cells -- DC-SIGN dendritic cell-specific intercellular adhesion molecule (ICAM)-3-grabbing nonintegrin -- DTT Dithiothreitol -- FAs focal adhesions -- FAK focal adhesion kinase -- GITs G-protein-coupled receptor kinase-interacting proteins -- GWAS genome-wide association studies -- HRP horseradish peroxidase -- MΦ macrophages -- Mtb Mycobacterium tuberculosis -- NK cells natural killer cells -- PMA phorbol 12-myristate 13-acetate -- PMSF Phenylmethanesulfonyl fluoride -- qRT-PCR quantitative reverse transcription-PCR -- SNP single-nucleotide polymorphism -- SMAPs stromal membrane-associated GTPase-activating proteins -- TB Tuberculosis; 616.995
• DOI: 10.1016/j.tube.2021.102090
• Languages: English
• ISSNs: 1472-9792

Abstract

Abstract: Tuberculosis is initiated by the entry of Mycobacterium tuberculosis (Mtb) into macrophages in the lungs. A study of the cellular factors responsible for the entry of Mtb into host cells will potentially benefit the development of therapeutic treatments or preventive agents against Mtb infection. Using human THP1-derived macrophages as a model, we found that infection of Mtb H37Ra transiently reduced the level of ASAP1, an ADP ribosylation factor (Arf)-GTPase activating protein. Furthermore, knockdown of ASAP1 increased the efficiency of H37Ra entry into the cell and altered the status of actin remodeling as indicated by the enhanced aggregation of F-actin and the increased numbers of vinculin- and paxillin-rich puncta. Collectively, the results in this report identified ASAP1 as a regulator controlling the entry of Mtb H37Ra into macrophage by remodeling actin cytoskeleton. Highlights: Mtb H37Ra infection reduces ASAP1 in THP1-derived macrophage. Knockdown of ASAP1 increases the efficiency of Mtb H37Ra entry into the cell. Knockdown of ASAP1 alters actin remodeling. ASAP1 regulates the entry of Mtb H37Ra into macrophage.