UCアーバインの研究チームが脳の形成に重要なグリコシル化酵素を同定(UC Irvine research team identifies glycosylation enzyme critical in brain formation)


2023-05-16 カリフォルニア大学校アーバイン校(UCI)

◆「Stem Cell Reports」誌に掲載されたこの研究では、糖鎖化中にMGAT5酵素がニューロンとアストロサイトの形成を重要に調節していることが明らかになりました。MGAT5を持たない神経幹細胞は、脳の発達初期段階でより多くのニューロンと少ないアストロサイトを生成し、その構造を変化させます。これらの変化は、異常な社会的相互作用や反復行動などの後の異常な行動パターンに寄与する可能性があります。


MGAT5を介したN-グリコシル化による神経幹細胞分化と脳発達の制御 Regulation of neural stem cell differentiation and brain development by MGAT5-mediated N-glycosylation

Andrew R. Yale,Estelle Kim,Brenda Gutierrez,J. Nicole Hanamoto,Nicole S. Lav,Jamison L. Nourse,Marc Salvatus,Robert F. Hunt,Edwin S. Monuki,Lisa A. Flanagan
Stem Cell Reports  Published:May 11, 2023

Figure thumbnail fx1


•Glycosylation enzyme MGAT5 produces branched N-glycans and influences stem cell fate
•Loss of branching increases neuron differentiation and decreases astrocytes in vitro
•Neuron differentiation in vivo is accelerated when branching is lost
•Accelerated differentiation depletes progenitors, altering cortical neuron layers


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.