title: Polypeptide N-Acetylgalactosaminyltransferase 13 Contributes to Neurogenesis via Stabilizing the Mucin-type O-Glycoprotein Podoplanin.
abstract: Mucin-type O-glycosylation is initiated by an evolutionarily conserved family of polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts). Previously, it was reported that ppGalNAc-T13 is restrictively expressed at a high level in the brain. Here we provide evidence for the critical role of ppGalNAc-T13 in neural differentiation. In detail, we show that the expression of ppGalNAc-T13 was dramatically up-regulated during early neurogenesis in mouse embryonic brains. Similar changes were also observed in cell models of neuronal differentiation by using either primary mouse cortical neural precursor cells or murine embryonal carcinoma P19 cells. Knockout of ppGalNAc-T13 in P19 cells suppressed not only neural induction but also neuronal differentiation. These effects are at least partly mediated by the mucin-type O-glycoprotein podoplanin (PDPN), as knockdown of PDPN led to a similar inhibition of neuronal differentiation and PDPN was significantly reduced at the posttranscriptional level after ppGalNAc-T13 knockout. Further data demonstrate that PDPN acts as a substrate of ppGalNAc-T13 and that the ppGalNAc-T13-mediated O-glycosylation on PDPN is important for its stability. Taken together, this study suggests that ppGalNAc-T13 contributes to neuronal differentiation through glycosylating and stabilizing PDPN, which provides insights into the regulatory roles of O-glycosylation in mammalian neural development.
authors.affiliation: From the Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
authors.forename: Yingjiao
authors.initials: Y
authors.lastname: Xu
authors.affiliation: From the Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Pang
authors.affiliation: From the Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
authors.forename: Jishun
authors.initials: J
authors.lastname: Lu
authors.affiliation: From the Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China.
authors.forename: Aidong
authors.initials: A
authors.lastname: Shan
authors.affiliation: From the Ministry of Education Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China yanzhang2006@sjtu.edu.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001921:Brain / Q000196:embryology / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism; D055495:Neurogenesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D014158:Transcription, Genetic; D000098853:Podoplanin
chemical_list: D008562:Membrane Glycoproteins; D017350:N-Acetylgalactosaminyltransferases; D034741:RNA, Small Interfering; C490441:Pdpn protein, mouse; D000098853:Podoplanin; C470848:UDP-N-acetyl-alpha-D-galactosamine polypeptide N-acetylgalactosaminyltransferase 13, mouse
keywords: Galnt13; glycoprotein; glycosylation; glycosyltransferase; mucin-type O-glycoprotein; neurodifferentiation; neuronal differentiation; podoplanin; ppGalNAc-T13; protein stability