Mannose receptor (MRC1) mediates uptake of dextran by bone marrow-derived macrophages.

IF 3.1 3区 生物学 Q3 CELL BIOLOGY
Molecular Biology of the Cell Pub Date : 2024-12-01 Epub Date: 2024-11-06 DOI:10.1091/mbc.E24-08-0355
Jared Wollman, Kevin Wanniarachchi, Bijaya Pradhan, Lu Huang, Jason G Kerkvliet, Adam D Hoppe, Natalie W Thiex
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引用次数: 0

Abstract

Macrophages survey their environment using receptor-mediated endocytosis and pinocytosis. Receptor-mediated endocytosis allows internalization of specific ligands, whereas pinocytosis nonselectively internalizes extracellular fluids and solutes. CRISPR/Cas9 whole-genome screens were used to identify genes regulating constitutive and growth factor-stimulated dextran uptake in murine bone marrow-derived macrophages (BMDM). The mannose receptor c-type 1 (MRC1/CD206) was a top hit in the screen. Targeted gene disruptions of Mrc1 reduced dextran uptake but had little effect on fluid-phase uptake of Lucifer yellow. Other screen hits also differentially affected the uptake of dextran and Lucifer yellow, indicating internalization by separate mechanisms. Visualization of dextran and Lucifer yellow uptake by microscopy showed enrichment of dextran in small puncta, which was inhibitable by mannan, a ligand of MRC1. In contrast, Lucifer yellow predominantly was internalized in larger macropinosomes. In addition, IL4-treated BMDMs internalized more dextran than untreated BMDM correlating with increased MRC1 expression. Therefore, dextran is not an effective marker for pinocytosis in BMDMs since it is internalized by receptor-mediated process. Numerous genes that regulate dextran internalization in primary murine macrophages were identified in the whole-genome screens, which can inform understanding of the regulation of MRC1 expression and MRC1-mediated uptake in macrophages.

甘露糖受体(MRC1)介导骨髓巨噬细胞对葡聚糖的吸收。
巨噬细胞利用受体介导的内吞和针吞来检测周围环境。受体介导的内吞作用可使特定配体内化,而针吞作用则可非选择性地使细胞外液和溶质内化。研究人员利用 CRISPR/Cas9 全基因组筛选技术鉴定了调节小鼠骨髓衍生巨噬细胞(BMDM)构成性葡聚糖摄取和生长因子刺激性葡聚糖摄取的基因。甘露糖受体 c 型 1(MRC1/CD206)是筛选中的热门基因。Mrc1的靶向基因干扰会减少葡聚糖的摄取,但对荧光黄的液相摄取影响不大。其他筛选结果也对葡聚糖和荧光黄的吸收产生了不同的影响,这表明它们是通过不同的机制内化的。用显微镜观察葡聚糖和荧光黄的摄取显示,葡聚糖富集在小点上,MRC1 的配体甘露聚糖可抑制这种富集。与此相反,Lucifer 黄则主要在较大的大胞体中被内化。此外,经 IL4 处理的 BMDM 比未经处理的 BMDM 内化更多的葡聚糖,这与 MRC1 表达的增加有关。因此,葡聚糖不是 BMDMs 针吞作用的有效标记物,因为它是通过受体介导的过程内化的。在全基因组筛选中发现了许多调控原代小鼠巨噬细胞右旋糖酐内化的基因,这些基因可以帮助人们了解巨噬细胞中 MRC1 表达的调控和 MRC1 介导的摄取。
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来源期刊
Molecular Biology of the Cell
Molecular Biology of the Cell 生物-细胞生物学
CiteScore
6.00
自引率
6.10%
发文量
402
审稿时长
2 months
期刊介绍: MBoC publishes research articles that present conceptual advances of broad interest and significance within all areas of cell, molecular, and developmental biology. We welcome manuscripts that describe advances with applications across topics including but not limited to: cell growth and division; nuclear and cytoskeletal processes; membrane trafficking and autophagy; organelle biology; quantitative cell biology; physical cell biology and mechanobiology; cell signaling; stem cell biology and development; cancer biology; cellular immunology and microbial pathogenesis; cellular neurobiology; prokaryotic cell biology; and cell biology of disease.
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