Discovery and characterization of a neuroligin-3 binding partner in gliomas and oligodendrocyte progenitors
Abstract/Contents
- Abstract
- Gliomas exhibit diverse genetic aberrations, spatiotemporal growth patterns and clinical outcomes, but are commonly regulated by a dynamic and multifaceted microenvironment that includes neurons. These neurons support glioma growth in part via shed or secreted trophic factors. Neuroligin-3 (NLGN3) is one such factor that functions as a critical microenvironmental determinant of low- and high-grade glioma growth, but its cognate binding partner on glioma cells has thus far eluded identification. Here, we establish that neuronal activity-induced shedding of NLGN3 ectodomains is detected by gliomas and normal oligodendrocyte precursors via binding to chondroitin sulfate proteoglycan 4 (CSPG4). Unexpectedly, NLGN3 binding triggers CSPG4 proteolysis and intracellular signaling that promotes growth of gliomas and inhibits differentiation of healthy oligodendrocyte precursors. Our results provide insight into how glioma cells and their normal counterparts sense, translate and respond to neuronal activity in their microenvironment and suggest a way forward in therapeutically targeting this signaling axis.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2021; ©2021 |
| Publication date | 2021; 2021 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Gillespie, Shawn Michael |
|---|---|
| Degree supervisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Monje-Deisseroth, Michelle |
| Thesis advisor | Ting, Alice Y |
| Thesis advisor | Zuchero, J |
| Thesis advisor | van Rechem, Capucine |
| Degree committee member | Ting, Alice Y |
| Degree committee member | Zuchero, J |
| Degree committee member | van Rechem, Capucine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Shawn Michael Gillespie. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2021. |
| Location | https://purl.stanford.edu/fd551sw7936 |
Access conditions
- Copyright
- © 2021 by Shawn Michael Gillespie
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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