首页|Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

Fucosyltransferase 8 regulates adult neurogenesis and cognition of mice by modulating the Itga6-PI3K/Akt signaling pathway

扫码查看
Fucosyltransferase 8(Fut8)and core fucosylation play critical roles in regulating various biological processes,including immune response,signal transduction,proteasomal degradation,and energy metabolism.However,the function and underlying mechanism of Fut8 and core fucosylation in regulating adult neurogenesis remains unknown.We have shown that Fut8 and core fucosylation display dynamic features during the differentiation of adult neural stem/progenitor cells(aNSPCs)and postnatal brain development.Fut8 depletion reduces the proliferation of aNSPCs and inhibits neuronal differentiation of aNSPCs in vitro and in vivo,respectively.Additionally,Fut8 deficiency impairs learning and memory in mice.Mechanistically,Fut8 directly interacts with integrin a6(Itga6),an upstream regulator of the PI3k-Akt signaling pathway,and catalyzes core fucosylation of Itga6.Deletion of Fut8 enhances the ubiquitination of Itga6 by promoting the binding of ubiquitin ligase Trim21 to Itga6.Low levels of Itga6 inhibit the activity of the PI3K/Akt signaling pathway.Moreover,the Akt agonist SC79 can rescue neurogenic and behavioral deficits caused by Fut8 deficiency.In summary,our study uncovers an essential function of Fut8 and core fucosylation in regulating adult neurogenesis and sheds light on the underlying mechanisms.

Fut8adult neural stem/progenitor cellsneurogenesisItga6PI3K/Akt

Hongfeng Guo、Qihang Sun、Xiaoli Huang、Xiaohao Wang、Feng Zhang、Wenzheng Qu、Jinling Liu、Xuejun Cheng、Qiang Zhu、Wen Yi、Qiang Shu、Xuekun Li

展开 >

The Children's Hospital,National Clinical Research Center for Child Health,School of Medicine,Zhejiang University,Hangzhou 310052,China

The Institute of Translational Medicine,School of Medicine,Zhejiang University,Hangzhou 310029,China

College of Life Sciences,Zhejiang University,Hangzhou 310058,China

Binjiang Institute of Zhejiang University,Hangzhou 310053,China

Zhejiang University Cancer Center,Zhejiang University,Hangzhou 310029,China

展开 >

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaCentral Guiding Fund for Local Science and Technology Development ProjectsNational Key Research and Development Program of China

92049108823711822023ZY10582017YFE0196600

2024

中国科学:生命科学(英文版)
中国科学院

中国科学:生命科学(英文版)

CSTPCD
影响因子:0.806
ISSN:1674-7305
年,卷(期):2024.67(7)