GDE3 regulates oligodendrocyte precursor proliferation via release of soluble CNTFRα.
Animals
Cell Membrane
/ metabolism
Cell Proliferation
Ciliary Neurotrophic Factor
/ metabolism
Ciliary Neurotrophic Factor Receptor alpha Subunit
/ metabolism
Cytokines
/ metabolism
Extracellular Vesicles
/ metabolism
Gene Deletion
HEK293 Cells
Humans
Mice
Oligodendrocyte Precursor Cells
/ cytology
Phosphoric Diester Hydrolases
/ metabolism
Signal Transduction
Solubility
Spinal Cord
/ embryology
CNTF
CNTFRα
GDE3 (GDPD2)
Mouse
Oligodendrocyte precursor
Proliferation
Journal
Development (Cambridge, England)
ISSN: 1477-9129
Titre abrégé: Development
Pays: England
ID NLM: 8701744
Informations de publication
Date de publication:
23 01 2020
23 01 2020
Historique:
received:
20
05
2019
accepted:
23
12
2019
pubmed:
15
1
2020
medline:
3
7
2020
entrez:
15
1
2020
Statut:
epublish
Résumé
Oligodendrocyte development is tightly controlled by extrinsic signals; however, mechanisms that modulate cellular responses to these factors remain unclear. Six-transmembrane glycerophosphodiester phosphodiesterases (GDEs) are emerging as central regulators of cellular differentiation via their ability to shed glycosylphosphatidylinositol (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 ciliary neurotrophic factor (CNTF)-mediated signaling through release of CNTFRα, the ligand-binding component of the CNTF-receptor multiprotein complex, which can function as a soluble factor to activate CNTF signaling. GDE3 releases soluble 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 regulation of OPC proliferation through release of CNTFRα.
Identifiants
pubmed: 31932351
pii: dev.180695
doi: 10.1242/dev.180695
pmc: PMC6983723
pii:
doi:
Substances chimiques
Ciliary Neurotrophic Factor
0
Ciliary Neurotrophic Factor Receptor alpha Subunit
0
Cytokines
0
Phosphoric Diester Hydrolases
EC 3.1.4.-
glycerophosphodiester phosphodiesterase
EC 3.1.4.46
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NINDS NIH HHS
ID : P30 NS050274
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS046336
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007445
Pays : United States
Informations de copyright
© 2020. Published by The Company of Biologists Ltd.
Déclaration de conflit d'intérêts
Competing interestsThe authors declare no competing or financial interests.
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