Exosome-Filopodia Interactions

外泌体-丝状伪足相互作用

基本信息

批准号：
9324393
负责人：
DONNA J WEBB
金额：
$ 3.91万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-02-05 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9324393
关键词：
Actins Adhesions Adhesives Back Behavior Binding Proteins Biogenesis Biological Biological Assay Biological Markers Biological Process Brain Cancer Control Cell Communication Cell Polarity Cell physiology Cells Clinical Coculture Techniques Communication Complex Data Dendritic Cells Dendritic Spines Development Devices Disease Docking Endoglin Endosomes Endothelial Cells Environment Epithelial Cells Exhibits Fibroblasts Filopodia Health Hippocampus (Brain)Human In Vitro Investigation Lead Malignant Neoplasms Mediating Mediator of activation protein Melanoma Cell Modification Molecular Monitor Mus Neonatal Neoplasm Metastasis Neurons Physiological Physiological Processes Process Proteins Proteomics RNA Reporting Reticulocytes Role Scientist Site Structure Synapses System TGF beta type III receptor Testing Therapeutic Tissues Transforming Growth Factor beta Western Blotting Work Wound Healing angiogenesis autocrine base cancer cell cell behavior cell motility cell type clinical biomarkers disorder control exosome experimental study extracellular extracellular vesicles genetic manipulation imaging probe immunological synapse in vivo interest late endosome microvesicles migration nervous system disorder neuron development novel novel therapeutic intervention postsynaptic public health relevance receptor stem cell fate synaptogenesis tool trafficking

项目摘要

DESCRIPTION (provided by applicant): Exosomes are small late endosome-derived extracellular vesicles that carry bioactive protein and RNA molecules and modulate cell behavior. Recent data indicate that a wide variety of cells, including cancer cells and neurons, secrete exosomes. Furthermore, preliminary reports indicate that secreted exosomes critically contribute to several physiological processes, including invasion and motility, stem cell fate, and angiogenesis. However, the specific biological effects of exosomes on cells are poorly understood. We recently identified invasive actin-based protrusions called invadopodia as specific docking sites for exosome-containing multivesicular endosomes (MVE) and showed that exosome secretion controls invadopodia biogenesis and activity. Our further investigations have uncovered a fundamental role for exosomes in regulating the formation of additional related actin-based motility structures: adhesions, and filopodia. Exosomes appear to have a particularly potent effect on filopodia, which are adhesive actin-based protrusions that are important for directional sensing, cell polarity, cell movement, and cellular interactions. We therefore propose the central hypothesis that a key function of exosomes is to promote formation of filopodia and thereby control local cellular behaviors. We will test this hypothesis i both cancer cells and neurons because these cells exhibit robust filopodia and filopodia control key cellular behaviors. We will identify the temporal and functional relationship between exosome secretion and filopodia formation. We will identify molecular exosome cargos that control filopodia formation and maturation and determine the mechanisms by which they act. Finally, we will determine the role of exosomes in regulating complex filopodia-dependent processes, including synapse formation and directed migration both in vitro and in vivo.

描述（由适用提供）：外泌体是携带生物活性蛋白和RNA分子并调节细胞行为的小型内体衍生的细胞外蔬菜。最近的数据表明，包括癌细胞和神经元，包括秘密外泌体在内的各种细胞。此外，初步报告表明，分泌的外泌体严重促进了几种物理过程，包括入侵和运动，干细胞命运和血管生成。但是，外泌体对细胞的特定生物学作用知之甚少。我们最近确定了称为Invadopodia的侵入性肌动蛋白是含外泌体多细胞内体（MVE）的特定对接位点，并表明外泌体分泌控制Invadopodia生物发生和活性。我们的进一步研究发现了外泌体在确定基于其他相关肌动蛋白的运动结构的形成中的基本作用：粘连和丝状。外泌体似乎对丝状霉菌具有特别有效的作用，丝状霉菌是基于粘附肌动蛋白的蛋白，对于定向感应，细胞极性，细胞运动和细胞相互作用很重要。因此，我们提出了一个核心假设，即外泌体的关键功能是促进丝状虫的形成，从而控制局部细胞行为。我们将检验该假设I癌细胞和神经元，因为这些细胞表现出强大的丝状丝虫病和丝状控制关键细胞行为。我们将确定外泌体分泌与丝状形成之间的暂时和功能关系。我们将确定控制丝状形成和成熟的分子外泌体肉食，并确定它们作用的机制。最后，我们将确定外泌体在确定复杂的丝虫依赖性过程中的作用，包括突触形成和体外的定向迁移。