The Mechanisms Involved in Chemotaxis of Immune and Cancer Cells
免疫细胞和癌细胞趋化性的机制
基本信息
- 批准号:10272190
- 负责人:
- 金额:$ 59.08万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:
- 资助国家:美国
- 起止时间:至
- 项目状态:未结题
- 来源:
- 关键词:ActinsBacteriaCellsChemotactic FactorsChemotaxisCoupledDefectEscherichia coliExhibitsG-Protein-Coupled ReceptorsGTP-Binding ProteinsGoalsHumanHuman bodyIL8 geneImmobilizationImmuneImmunoglobulin GInvadedMediatingMolecularMusNatural ImmunityNeoplasm MetastasisOpsoninPhagocytesPhagocytosisPhosphorylationProtein Tyrosine KinaseProto-Oncogene Proteins c-aktReceptor Protein-Tyrosine KinasesSignal TransductionSurfaceWorkcancer cellcell motilitychemokinechemokine receptorcofilinfMet-Leu-Phe receptorfightingmigrationneutrophilpolymerizationreceptorresponsetrafficking
项目摘要
We several projects.
1. A dogma of innate immunity is that neutrophils use chemoattractant GPCRs to chase bacteria through chemotaxis and then use phagocytic receptors coupled with tyrosine kinases to destroy opsonized bacteria via phagocytosis. Our current work has changed this dogma by showing that G-protein-coupled formyl peptide receptors (FPRs) directly mediate neutrophil phagocytosis. Mouse neutrophils lacking formyl peptide receptors (Fpr1/2-/-) are defective in the phagocytosis of E. coli and the chemoattractant fMLP-coated beads. fMLP immobilized on the surface of a bead interacts with FPRs triggers a Ca2+ response, and induces actin polymerization to form a phagocytic cup for engulfment of the bead. Chemoattractant GPCR/Gi signaling and phagocytic receptor/tyrosine kinase signaling work independently to promote phagocytosis of beads coated with either chemoattractants or IgG opsonins. Thus, in addition to phagocytic receptor-mediated phagocytosis, neutrophils also utilize the chemoattractant GPCR/Gi signaling to mediate phagocytosis to fight invading bacteria (Wen etal, 2019).
2. Neutrophils sense and migrate through a large range of chemoattractant gradient through an adaptation mechanism. Here, we reveal CPARI, a negative regulator of Ras, that controls GPCR-stimulated Ras signaling in human neutrophils. Cells lacking CAPRI (caprikd) exhibit significantly increased phosphorylation of AKT, GSK3, and cofilin, leading to excessive actin polymerization and subsequent defects in neutrophil chemotaxis. The caprikd cells display chemotaxis defects only in high concentration, but not in low-concentration gradient, remarkably, show better chemotaxis in sub-responsive concentration of chemoattractant gradient due to their higher sensitivity. Taken together, we reveal that CAPRI controls GPCR-mediated adaptation and downshifts the sensitivity of neutrophils for Chemotaxis.
我们有几个项目。
1.先天免疫的一个信条是中性粒细胞使用趋化物GPCR通过趋化性追逐细菌,然后使用与酪氨酸激酶偶联的吞噬受体通过吞噬作用破坏调理的细菌。 我们目前的工作改变了这一教条,表明G蛋白偶联甲酰肽受体(FPRs)直接介导中性粒细胞吞噬。 缺乏甲酰肽受体(Fpr 1/2-/-)的小鼠中性粒细胞在E. coli和化学引诱物fMLP包被的珠粒。 固定在珠表面上的fMLP与FPR相互作用触发Ca 2+反应,并诱导肌动蛋白聚合以形成吞噬珠的吞噬杯。 化学引诱物GPCR/Gi信号传导和吞噬细胞受体/酪氨酸激酶信号传导独立地起作用以促进涂覆有化学引诱物或IgG调理素的珠粒的吞噬作用。 因此,除了吞噬受体介导的吞噬作用外,中性粒细胞还利用化学引诱物GPCR/Gi信号传导介导吞噬作用,以对抗入侵细菌(Wen埃塔尔,2019)。
2.中性粒细胞通过适应机制感知并迁移通过大范围的化学引诱物梯度。在这里,我们揭示了CPARI,Ras的负调节,控制GPCR刺激的Ras信号在人类中性粒细胞。缺乏卡普里(caprikd)的细胞表现出AKT,GSK 3和cofilin的磷酸化显著增加,导致过度的肌动蛋白聚合和随后的中性粒细胞趋化性缺陷。山羊细胞只在高浓度下表现出趋化性缺陷,而在低浓度梯度下则无趋化性缺陷,特别是在亚反应浓度的趋化梯度下,山羊细胞对趋化剂的敏感性更高,表现出更好的趋化性。总之,我们发现卡普里控制GPCR介导的适应和降低中性粒细胞趋化性的敏感性。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Tian Jin其他文献
Tian Jin的其他文献
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{{ truncateString('Tian Jin', 18)}}的其他基金
The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum
D. discoideum GPCR 介导的趋化机制
- 批准号:
10272094 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
Using FRET to Probe the Spatial Distributions of CD4, CX
使用 FRET 探测 CD4、CX 的空间分布
- 批准号:
7312953 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
G-protein Coupled Receptor Mediated Directional Sensing
G蛋白偶联受体介导的定向传感
- 批准号:
6987079 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum
D. discoideum GPCR 介导的趋化机制
- 批准号:
8745398 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
The Mechanisms Involved in Chemotaxis of Immune and Cancer Cells
免疫细胞和癌细胞趋化性的机制
- 批准号:
9566738 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
G-protein Coupled Receptor Mediated Chemoattractant Sensing and Phagocytosis
G 蛋白偶联受体介导的趋化剂感应和吞噬作用
- 批准号:
7732578 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
The mechanisms underlying the GPCR-mediated chemotaxis in D. discoideum
D. discoideum GPCR 介导的趋化机制
- 批准号:
9566620 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
G-protein Coupled Receptor Mediated Chemoattractant Sensing and Phagocytosis
G 蛋白偶联受体介导的趋化剂感应和吞噬作用
- 批准号:
8156943 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
Identification of co-receptor and components involved in the entry of SARS-CoV-2 using a quantitative phosphoproteomic approach
使用定量磷酸蛋白质组学方法鉴定参与 SARS-CoV-2 进入的共受体和成分
- 批准号:
10272278 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
FRET Probe of Spatial Distributions of CD4/CXCR/CCR5
CD4/CXCR/CCR5空间分布的FRET探针
- 批准号:
7196712 - 财政年份:
- 资助金额:
$ 59.08万 - 项目类别:
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