Alpha2,3-Sialylation regulates the stability of stem cell marker CD133.
CD133 is widely used as a marker for the isolation and characterization of normal and cancer stem cells. The dynamic alternation of CD133 glycosylation contributes to the isolation of normal and cancer stem cells, and is supposed to be associated with cell differentiation. Although CD133 has been identified as a N-glycosylated protein, the specific glycosylation status of CD133 remain unclear. Here, we found that CD133 could be sialylated in neural stem cells and glioma-initiating cells, and the sialyl residues attach to CD133 N-glycan terminal via alpha2,3-linkage. Furthermore, desialylation of CD133 by neuraminidase specifically accelerates its degradation in lysosomes-dependent pathway. Taken together, our results characterized CD133 as an alpha2,3-sialylated glycoprotein and revealed that the sialylation modification contributes to the stability of CD133 protein, providing clues to understanding the function of CD133 molecular and to understanding the utility of glycosylated CD133 epitopes in defining neural stem cells and tumour-initiating cells.
Zhou
Fengbiao
F
Key Laboratory of Glycoconjuates Research, Ministry of Public Health and Gene Research Center, Shanghai Medical College of Fudan University, Shanghai, 200032, People's Republic of China.
Cui
Chunhong
C
Ge
Yuqing
Y
Chen
Hong
H
Li
Qiuping
Q
Yang
Zhiyuan
Z
Wu
Guoqiang
G
Sun
Shuhui
S
Chen
Kangli
K
Gu
Jianxin
J
Jiang
Jianhai
J
Wei
Yuanyan
Y
D000071916:AC133 Antigen; D015703:Antigens, CD / Q000378:metabolism*; D015415:Biomarkers; D002460:Cell Line; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000166:cytology; D058953:Neural Stem Cells / Q000166:cytology; D009439:Neuraminidase / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D055550:Protein Stability; D013234:Stem Cells / Q000166:cytology*
D000071916:AC133 Antigen; D015703:Antigens, CD; D015415:Biomarkers; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D009439:Neuraminidase; D019158:N-Acetylneuraminic Acid