TY - JOUR
T1 - Loss of mucin-type O-glycans impairs the integrity of the glomerular filtration barrier in the mouse kidney
AU - Song, Kai
AU - Fu, Jianxin
AU - Song, Jianhua
AU - Herzog, Brett H.
AU - Bergstrom, Kirk
AU - Kondo, Yuji
AU - McDaniel, J. Michael
AU - McGee, Samuel
AU - Silasi-Mansat, Robert
AU - Lupu, Florea
AU - Chen, Hong
AU - Bagavant, Harini
AU - Xia, Lijun
N1 - Funding Information:
This work was supported by National Institutes of Health Grants GM114731, HL128390, HD083418, DK085691, HL093242, and HL118676; National Nat-ural Science Foundation of China Grants 81520108005, 81470825, and 81370617; Jiangsu Province Key Medical Center Grant ZX201102; and Sci-entist Development Grants from the American Heart Association 11SDG7410022 (to J. F.) and 17SDG33630161 (to K. S.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Funding Information:
2To whom correspondence should be addressed: Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, 825 N.E. 13th St., Oklahoma City, OK 73104. Tel.: 405-271-7892; Fax: 405-271-3137; E-mail: lijun-xia@omrf.org.
Funding Information:
From the ‡Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, the §Vascular Biology Program, Boston Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, the ¶Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104, the ‖Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu, China, and the **Department of Molecular Biology and Biochemistry, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104
Publisher Copyright:
© 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2017/10/6
Y1 - 2017/10/6
N2 - The kidney’s filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened, and surrounded by podocytes, specialized cells that support glomerular endothelial cells. Mucin-type core 1– derived O-glycans (O-glycans) are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1– derived O-glycans is catalyzed by the glycosyltransferase core 1 1,3-galactosyltrans-ferase (C1galt1). Here we report that neonatal or adult mice with inducible deletion of C1galt1 (iC1galt1/) exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O-glycans results in altered podocyte foot processes. Further analysis indicated that O-glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process–associated glycoprotein. Our results reveal a new function of O-glycosylation in the integrity of the glomerular filtration barrier.
AB - The kidney’s filtration activity is essential for removing toxins and waste products from the body. The vascular endothelial cells of the glomerulus are fenestrated, flattened, and surrounded by podocytes, specialized cells that support glomerular endothelial cells. Mucin-type core 1– derived O-glycans (O-glycans) are highly expressed on both glomerular capillary endothelial cells and their supporting podocytes, but their biological role is unclear. Biosynthesis of core 1– derived O-glycans is catalyzed by the glycosyltransferase core 1 1,3-galactosyltrans-ferase (C1galt1). Here we report that neonatal or adult mice with inducible deletion of C1galt1 (iC1galt1/) exhibit spontaneous proteinuria and rapidly progressing glomerulosclerosis. Ultrastructural analysis of the glomerular filtration barrier components revealed that loss of O-glycans results in altered podocyte foot processes. Further analysis indicated that O-glycan is essential for the normal signaling function of podocalyxin, a podocyte foot process–associated glycoprotein. Our results reveal a new function of O-glycosylation in the integrity of the glomerular filtration barrier.
UR - http://www.scopus.com/inward/record.url?scp=85030791842&partnerID=8YFLogxK
U2 - 10.1074/jbc.M117.798512
DO - 10.1074/jbc.M117.798512
M3 - Article
C2 - 28842487
AN - SCOPUS:85030791842
SN - 0021-9258
VL - 292
SP - 16491
EP - 16497
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 40
ER -