A naturally occurring transcript variant of MARCO reveals the SRCR domain is critical for function

Immunology and Cell Biology
Kyle E NovakowskiDawn M E Bowdish

Abstract

Macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor (cA-SR) that recognizes and phagocytoses a wide variety of pathogens. Most cA-SRs that contain a C-terminal scavenger receptor cysteine-rich (SRCR) domain use the proximal collagenous domain to bind ligands. In contrast, the role of the SRCR domain of MARCO in phagocytosis, adhesion and pro-inflammatory signaling is less clear. The discovery of a naturally occurring transcript variant lacking the SRCR domain, MARCOII, provided the opportunity to study the role of the SRCR domain of MARCO. We tested whether the SRCR domain is required for ligand binding, promoting downstream signaling and enhancing cellular adhesion. Unlike cells expressing full-length MARCO, ligand binding was abolished in MARCOII-expressing cells. Furthermore, co-expression of MARCO and MARCOII impaired phagocytic function, indicating that MARCOII acts as a dominant-negative variant. Unlike MARCO, expression of MARCOII did not enhance Toll-like receptor 2 (TLR2)-mediated pro-inflammatory signaling in response to bacterial stimulation. MARCO-expressing cells were more adherent and exhibited a dendritic-like phenotype, whereas MARCOII-expressing cells were less adherent and di...Continue Reading

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Citations

Aug 26, 2016·Immunological Reviews·Roni LevinJohnathan Canton
Nov 23, 2017·Molecular Biology and Evolution·Kyle E NovakowskiDawn M E Bowdish
Sep 28, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhigang LiJie Fan
May 28, 2019·Journal of Thrombosis and Haemostasis : JTH·Laura L SwystunDavid Lillicrap
Dec 3, 2020·International Journal of Molecular Sciences·Anna ChiariniIlaria Dal Prà
Jul 20, 2021·Advances in Wound Care·Kellen ChenGeoffrey C Gurtner

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Datasets Mentioned

BETA
CR603381

Methods Mentioned

BETA
PCR
electrophoresis
flow cytometry
transfection
co-Immunoprecipitation
transfecting
Scanning Electron Microscopy
density gradient centrifugation
size exclusion chromatography
dynamic light scattering

Software Mentioned

ImageJ
ImageQuant
FlowJo
Aceview
FACSDiva
GraphPad Prism
MARCO
OpenLab

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