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The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages

ABSTRACT: The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages

PROVIDER: PRJNA791287 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR17288786.fastq.gz	Fastqsanger.gz
	SRR17288787.fastq.gz	Fastqsanger.gz
	SRR17288788.fastq.gz	Fastqsanger.gz
	SRR17288789.fastq.gz	Fastqsanger.gz
	SRR17288790.fastq.gz	Fastqsanger.gz

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Similar Datasets

The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages

Project description:Many apoptotic thymocytes are generated during the course of T cell selection in the thymus, yet the machinery through which these dead cells are recognized and phagocytically cleared is incompletely understood. We find that the TAM receptor tyrosine kinases Axl and Mer, which are co-expressed by a specialized set of phagocytic thymic macrophages, are essential components of this machinery. Axl-/-Mertk-/- double mutant mice exhibited a marked accumulation of apoptotic cells during the time that autoreactive and nonreactive thymocytes die. Unexpectedly, the double mutants also displayed a profound deficit in the total number of phagocytic macrophages in the thymus, and concomitantly exhibited diminished expression of key non-TAM engulfment systems in the macrophages that remain. These previously unrecognized deficits were not confined to the thymus, and were also evident in the bone marrow and spleen. They had pleiotropic metabolic consequences for the double mutants, which included severe dysregulation of hemoglobin turnover, iron metabolism, and erythropoiesis.

2022-07-12 | GSE192363 | GEO

The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages

Project description:The TAM receptor tyrosine kinases Axl and Mer drive the phagocytic differentiation of tissue-resident macrophages

| PRJNA791287 | ENA

Microglia use TAM receptors to detect and engulf amyloid beta plaques

Project description:Two microglial TAM receptor tyrosine kinases - Axl and Mer - have been linked to Alzheimer’s disease, but their roles in disease have not been tested experimentally. We find that in Alzheimer’s disease and its mouse models, induced expression of Axl and Mer in amyloid plaque-associated microglia is coupled to induced plaque decoration by the TAM ligand Gas6 and its co-ligand phosphatidylserine. In the APP/PS1 mouse model of Alzheimer’s disease, sIngle cell RNAseq analysis comparing wild type microglia with those with Axl and Mer deficiency reveals a similar disease state transitional program of microglia but a dampened differential expression of numerous AD siganture genes in microglia lacking TAM receptors. In line with the transcriptomic data, using two-photon microscopy, we show that genetic ablation of Axl and Mer results in microglia that are unable to normally detect, respond to, organize, or phagocytose amyloid beta plaques. These major deficits notwithstanding, and contrary to expectation, TAM-deficient APP/PS1 mice develop fewer dense-core plaques than APP/PS1 mice with normal microglia. Our findings reveal that the TAM system is an essential mediator of microglial recognition and engulfment of amyloid plaques, and that TAM-driven microglial phagocytosis does not constrain, but rather promotes, plaque development.

2021-02-25 | GSE160523 | GEO

The TAM receptor tyrosine kinases Axl and Mer drive the maintenance of highly phagocytic macrophages.

Project description:Many apoptotic thymocytes are generated during the course of T cell selection in the thymus, yet the machinery through which these dead cells are recognized and phagocytically cleared is incompletely understood. We found that the TAM receptor tyrosine kinases Axl and Mer, which are co-expressed by a specialized set of phagocytic thymic macrophages, are essential components of this machinery. Mutant mice lacking Axl and Mer exhibited a marked accumulation of apoptotic cells during the time that autoreactive and nonreactive thymocytes normally die. Unexpectedly, these double mutants also displayed a profound deficit in the total number of highly phagocytic macrophages in the thymus, and concomitantly exhibited diminished expression of TIM-4, CD163, and other non-TAM phagocytic engulfment systems in the macrophages that remained. Importantly, these previously unrecognized deficits were not confined to the thymus, as they were also evident in the spleen and bone marrow. They had pleiotropic consequences for the double mutants, also previously unrecognized, which included dysregulation of hemoglobin turnover and iron metabolism leading to anemia.

| S-EPMC9373726 | biostudies-literature

Identification of AXL interactome by proximity-dependent protein identification (BioID)

Project description:AXL is a receptor tyrosine kinase (RTK) which, together with TYRO3 and MER, belongs to the TAM receptor family. A ligand for AXL is growth arrest specific 6 (GAS6), which is able to bind all three TAMs with the highest affinity for AXL. AXL is overexpressed in a variety of different cancers, which correlates with poor prognosis, metastasis and drug resistance. However, its biology is still not fully understood and data concerning proteins that interact with this receptor are almost completely lacking. To identify mechanisms underlying the role of GAS6-AXL signaling in cancer, we established an AXL interactome using proximity-dependent biotin identification (BioID) assay. Experiments were conducted in HEK293 cells and human glioblastoma LN229 cells, which do not express and express AXL, respectively. The Gene Ontology (GO) analysis of biological processes indicated enrichment of proteins implicated in cell junction organization, axonogenesis, supramolecular fiber organization, angiogenesis and actin-related processes in bot, non-stimulated and GAS6-stimulated samples. Importantly, in samples with activated AXL, proteins implicated in actin-related processes were overrepresented. Consistent with this, we found that GAS6 stimulation triggered actin remodeling manifested by intense membrane ruffling and macropinocytosis. Our study provides comprehensive data about proteins interacting with AXL. Thus, the obtained results will help to understand the biology of the AXL receptor, particularly with respect to its involvement in cancer invasion.

2021-06-28 | PXD017933 | Pride

Regulation of brain endothelial cell physiology by the TAM receptor tyrosine kinase Mer

Project description:Regulation of brain endothelial cell physiology by the TAM receptor tyrosine kinase Mer

| PRJNA935761 | ENA

Regulation of brain endothelial cell physiology by the TAM receptor tyrosine kinase Mer

Project description:The receptor tyrosine kinase Mer (gene name Mertk) acts in vascular endothelial cells (ECs) to tighten the blood-brain barrier (BBB) subsequent to viral infection. Correspondingly, we found that Mer regulates the expression and activity of a large cohort of cytoskeletal and BBB proteins, together with endothelial nitric oxide synthase, in brain ECs. We further found that Mer controls the expression of multiple angiogenic genes, and that EC-specific Mertk gene inactivation results in perturbed vascular sprouting and a compromised BBB after induced photothrombotic stroke. Unexpectedly, stroke lesions in the brain were also markedly reduced in the absence of EC Mer, which was linked to reduced plasma expression of fibrinogen, prothrombin, and other effectors of blood coagulation. Together, these results demonstrate that Mer is a central regulator of angiogenesis, BBB integrity, and blood coagulation in the mature vasculature. They may also account for disease severity following infection with the coronavirus SARS-CoV-2.

2023-08-24 | GSE225474 | GEO

Expression data from knockdown of Tyro3 in hepatocellular carcinoma

Project description:Tyro3 is a member of the TAM (Tyro3, Axl and Mer) receptor family. In this study, we want to know potential association between Tyro3 expression in HCC and the involved signaling pathway.

2018-09-04 | GSE119388 | GEO

In vitro phosphorylation of trypsin-digested K562 cell lysate by TAM family kinases

Project description:K562 cell lysate was digested with trypsin, dephosphorylated with lambda phosphatase, and treated in an in vitro kinase reaction with Axl, Mer or Tyro3 kinase, alongside a control reaction for each that contained no kinase. Samples were phosphoenriched with the SMOAC approach (TiO2 and FeNTA) and analyzed on an Orbitrap-Velos. Peptides were identified using PEAKS Studio X Pro.

2023-08-29 | MSV000092784 | MassIVE

Differential regulation of hepatic physiology and injury by the TAM receptors Axl and Mer.

Project description:Genome-wide association studies have implicated the TAM receptor tyrosine kinase (RTK) Mer in liver disease, yet our understanding of the role that Mer and its related RTKs Tyro3 and Axl play in liver homeostasis and the response to acute injury is limited. We find that Mer and Axl are most prominently expressed in hepatic Kupffer and endothelial cells and that as mice lacking these RTKs age, they develop profound liver disease characterized by apoptotic cell accumulation and immune activation. We further find that Mer is critical to the phagocytosis of apoptotic hepatocytes generated in settings of acute hepatic injury, and that Mer and Axl act in concert to inhibit cytokine production in these settings. In contrast, we find that Axl is uniquely important in mitigating liver damage during acetaminophen intoxication. Although Mer and Axl are protective in acute injury models, we find that Axl exacerbates fibrosis in a model of chronic injury. These divergent effects have important implications for the design and implementation of TAM-directed therapeutics that might target these RTKs in the liver.

| S-EPMC7335405 | biostudies-literature

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