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Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation.


ABSTRACT: Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specific changes in NSPC differentiation in vitro and in vivo. Mgat5 homozygous null NSPCs in culture formed more neurons and fewer astrocytes compared with wild-type controls. In the brain cerebral cortex, loss of MGAT5 caused accelerated neuronal differentiation. Rapid neuronal differentiation led to depletion of cells in the NSPC niche, resulting in a shift in cortical neuron layers in Mgat5 null mice. Glycosylation enzyme MGAT5 plays a critical and previously unrecognized role in cell differentiation and early brain development.

SUBMITTER: Yale AR 

PROVIDER: S-EPMC10277816 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation.

Yale Andrew R AR   Kim Estelle E   Gutierrez Brenda B   Hanamoto J Nicole JN   Lav Nicole S NS   Nourse Jamison L JL   Salvatus Marc M   Hunt Robert F RF   Monuki Edwin S ES   Flanagan Lisa A LA  

Stem cell reports 20230511 6


Undifferentiated neural stem and progenitor cells (NSPCs) encounter extracellular signals that bind plasma membrane proteins and influence differentiation. Membrane proteins are regulated by N-linked glycosylation, making it possible that glycosylation plays a critical role in cell differentiation. We assessed enzymes that control N-glycosylation in NSPCs and found that loss of the enzyme responsible for generating β1,6-branched N-glycans, N-acetylglucosaminyltransferase V (MGAT5), led to specif  ...[more]

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