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Kim, Jae-Ick
Neural Circuit and Neurodegenerative Disease Lab.
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Functional role of O-GlcNAcylation in serotonergic neurons

Lee, Ha-EunCho, EunjeongLee, Byeong EunKim, Hye YunKim, Hyun-JinKim, Jae-Ick
Issued Date
KSBMB International Conference 2022
Serotonergic neurons in the raphe nuclei project their axon fibers to almost all brain regions and are essential for
diverse brain functions. Despite this functional significance, however, there still remains a good deal of uncertainty
as to how serotonergic neurons and their activities are regulated at the molecular level. O-GlcNAcylation is a posttranslational
modification that attaches O-linked β-N-acetylglucosamine (O-GlcNAc) to serine/threonine residue of
proteins. O-GlcNAcylation plays a critical role in key cellular processes. Notably, O-GlcNAcylation and two related
enzymes, O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), are highly enriched in the brain and numerous
neuronal proteins are known to be O-GlcNAcylated, while our understanding of the functional role of O-GlcNAcylation
remains rudimentary in the brain. In this study, we investigated the functional role of O-GlcNAcylation in raphe
serotonergic neurons. We found that genetic down-regulation of O-GlcNAcylation in serotonergic neurons causes a
marked effect on cell survival. In addition, genetic up-regulation of O-GlcNAcylation led to the changes in synaptic
functions of serotonergic neurons and serotonin-related behaviors. Given the recent findings about molecular and
cellular heterogeneity of raphe serotonergic neurons, our findings will provide new insights into the molecular
mechanisms by which serotonergic neurons and serotonin-related behaviors are controlled in the brain.
Korean Society for Biochemistry and Molecular Biology


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