Astrocyte Exosomes are a Potential Delivery System for Paracrine Notch Signaling

Conference Year

January 2019

Abstract

Exosomes are small extracellular vesicles secreted by many cell types and have been found to contain a wide assortment of cargo ranging from RNA species to full-length transmembrane receptors. Accordingly, exosomes have garnered significant research attention in recent years with respect to their potential both as disease biomarkers and as vehicles for cell signaling. We have demonstrated the presence of Notch1 Intracellular Domain (NICD), a cleaved portion of the Notch1 receptor necessary for signal propagation, within exosomes secreted from astrocytes. As the canonical understanding of Notch signaling presupposes the necessity of cell-cell contact for signal initiation, this observation suggests that a novel, paracrine method of Notch signal propagation may be taking place via exosome secretion. Given the ubiquity and powerful downstream effects of Notch signaling, this observation has significant implications in developmental neuroscience, the cellular response to injury, and stem cell biology. Future experiments will seek to demonstrate the functional competence of these extracellular Notch signals with respect to their ability to carry out signal transduction as they do in their canonical context as well as characterize other potential exosomal cargo.

Primary Faculty Mentor Name

Jeffrey Spees

Status

Graduate

Student College

College of Arts and Sciences

Program/Major

Neuroscience

Primary Research Category

Health Sciences

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Astrocyte Exosomes are a Potential Delivery System for Paracrine Notch Signaling

Exosomes are small extracellular vesicles secreted by many cell types and have been found to contain a wide assortment of cargo ranging from RNA species to full-length transmembrane receptors. Accordingly, exosomes have garnered significant research attention in recent years with respect to their potential both as disease biomarkers and as vehicles for cell signaling. We have demonstrated the presence of Notch1 Intracellular Domain (NICD), a cleaved portion of the Notch1 receptor necessary for signal propagation, within exosomes secreted from astrocytes. As the canonical understanding of Notch signaling presupposes the necessity of cell-cell contact for signal initiation, this observation suggests that a novel, paracrine method of Notch signal propagation may be taking place via exosome secretion. Given the ubiquity and powerful downstream effects of Notch signaling, this observation has significant implications in developmental neuroscience, the cellular response to injury, and stem cell biology. Future experiments will seek to demonstrate the functional competence of these extracellular Notch signals with respect to their ability to carry out signal transduction as they do in their canonical context as well as characterize other potential exosomal cargo.