GDE3 Function in Oligodendrocyte Precursor Cell Proliferation

Simple item page
dc.contributor.advisorKolodkin, Alex
dc.contributor.committeeMemberBergles, Dwight
dc.contributor.committeeMemberBlackshaw, Seth
dc.creatorDobrowolski, Mateusz
dc.date.accessioned2019-07-30T01:37:07Z
dc.date.created2019-05
dc.date.issued2018-11-12
dc.date.submittedMay 2019
dc.date.updated2019-07-30T01:37:08Z
dc.description.abstractOligodendrocyte specification, proliferation and differentiation are tightly controlled by extrinsic signals; however, proteins that modulate cellular response to these factors remain unclear. Six-transmembrane GDEs are emerging as central regulators of cellular differentiation via their unique ability to shed GPI-anchored proteins from the cell surface. We show here that GDE3 controls the pace of oligodendrocyte generation by negatively regulating oligodendrocyte precursor cell (OPC) proliferation. GDE3 inhibits OPC proliferation by stimulating CNTF-mediated signaling through release of CNTFRα, the ligand-binding component of the gp130/LIFRβ CNTF receptor complex that can function as a soluble factor. GDE3 releases CNTFRα by GPI-anchor cleavage from the plasma membrane and from extracellular vesicles (EVs) after co-recruitment of CNTFRα in EVs. These studies uncover new physiological roles for GDE3 in gliogenesis and identify GDE3 as a key regulator of CNTF-dependent inhibition of OPC proliferation through bi-modal release of CNTFRα.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://jhir.library.jhu.edu/handle/1774.2/61426
dc.language.isoen_US
dc.publisherJohns Hopkins University
dc.publisher.countryUSA
dc.subjectoligodendrocyte
dc.subjectproliferation
dc.subjectGDE3
dc.subjectGDPD2
dc.subjectGPI-anchor
dc.subjectCNTFRα
dc.subjectCNTF
dc.subjectextracellular vesicle
dc.subjectexosome
dc.subject
dc.titleGDE3 Function in Oligodendrocyte Precursor Cell Proliferation
dc.typeThesis
dc.type.materialtext
local.embargo.lift2021-05-01
local.embargo.terms2021-05-01
thesis.degree.departmentBiochemistry, Cellular and Molecular Biology
thesis.degree.disciplineNeuroscience
thesis.degree.grantorJohns Hopkins University
thesis.degree.grantorSchool of Medicine
thesis.degree.levelDoctoral
thesis.degree.namePh.D.
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
DOBROWOLSKI-DISSERTATION-2019.pdf
Size:
4.71 MB
Format:
Adobe Portable Document Format
Download
License bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
LICENSE.txt
Size:
2.68 KB
Format:
Plain Text
Description:
Download
Collections
ETD -- Doctoral Dissertations