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Glia maturation factor-gamma modulation of signaling pathways in macrophages

巨噬细胞信号通路的神经胶质成熟因子-γ调节

基本信息

批准号：
8939812
负责人：
GRIFFIN RODGERS
金额：
$ 32.92万
依托单位：
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
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：
https://reporter.nih.gov/project-details/8939812
关键词：
Address Back Biological Process Blood Categories Cell Adhesion Cell Lineage Cell membrane Cells Chemotactic Factors Clinic Complex Data Development Disease Dysmyelopoietic Syndromes Early Endosome Erythroid Exocytosis Exposure to Gene Expression Profile Gene Expression Profiling Genes Genetic Transcription Glia Maturation Factor Global Change Granulopoiesis Hematopoiesis Hematopoietic Hematopoietic stem cells Human Integrins Leukemic Cell Leukocytes Liquid substance Maps Methods Molecular Molecular Profiling Mutation Myelogenous Myeloproliferation Oncogenes Ontology Population Proteins Recycling Rest Signal Pathway Stem cells Stromal Cell-Derived Factor 1 Structure Suggestion System T-Lymphocyte Techniques Time Trees Two-Dimensional Gel Electrophoresis cell type glia maturation factor gamma late endosome leukemia macrophage migration monocyte neutrophil novel progenitor stem tool two-dimensional

项目摘要

Leukocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle. Glia maturation factor-γ (GMFG), a novel regulator of the Arp2/3 complex, has been shown to be required for efficient directional migration of neutrophils and T-lymphocytes. Here, we investigated whether GMFG has similar effects on human monocyte migration, as well as the cellular mechanisms involved in GMFG action. We found that GMFG localizes to early endosomes (where it colocalizes with β1-integrins) and late endosomes, as well as the endocytic recycling compartment. Knockdown of GMFG in monocytes retarded the efficient rapid recycling of β1-integrins back to the plasma membrane and dramatically increased their degradation in both resting as well as fMLF- or SDF-1α-stimulated monocytes. Importantly, knockdown of GMFG results in reduced cell adhesion, and impaired directional migration of monocytes toward the chemoattractants fMLF and SDF-1α. These data identify GMFG as a molecular switch controlling β1-integrin recycling and its degradation to promote efficient monocyte migration.

白细胞迁移需要整合素的动态再分配，通过调节胞内-胞外循环。神经胶质成熟因子（Glia mature factor-&#947； GMFG）是Arp2/3复合物的一种新型调节剂，已被证明是中性粒细胞和t淋巴细胞有效定向迁移所必需的。在这里，我们研究了GMFG是否对人类单核细胞迁移有类似的影响，以及GMFG作用所涉及的细胞机制。我们发现GMFG定位于早期核内体（与1-整合素共定位）和晚期核内体，以及内吞循环室。单核细胞中GMFG的敲低延缓了1-整合素快速有效地再循环回到质膜，并在静止以及fMLF-或sdf -1 -刺激的单核细胞中显著增加了它们的降解。重要的是，敲低GMFG导致细胞粘附减少，单核细胞向趋化剂fMLF和sdf -1的定向迁移受损。这些数据确定GMFG是控制1-整合素循环及其降解以促进单核细胞有效迁移的分子开关。