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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.