N-acetylglucosaminyltransferase III expression is regulated by cell-cell adhesion via the E-cadherin-catenin-actin complex.
Recently, our research group investigated the effects of cell-cell interactions on N-linked oligosaccharides (N-glycans). We found that N-acetylglucosaminyltransferase III (GnT-III) activity, and thus, the enzyme product-bisected N-glycans were induced in cells cultured under dense condition in an E-cadherin-dependent manner. To further explore the underlying molecular mechanism, we examined the effects of alpha-catenin, which is a component of the E-cadherin-catenin complex that can bind to actin cytoskeleton, on the regulation of GnT-III expression in the human colon carcinoma DLD-1 cells. GnT-III activity was not substantially increased in cells cultured under dense conditions, compared with those cultured under sparse conditions. However, restoration of alpha-catenin gene to DLD-1 cells resulted in a significant increase in GnT-III activity and in production of the bisected N-glycans, which were detected by E(4)-PHA, suggesting that the E-cadherin-catenin complex is required for the induction. Moreover, treatment with cytochalasin D, an inhibitor of F-actin polymerization, completely blocked the upregulation of GnT-III expression in the dense culture. Taken together, these results strongly suggest that GnT-III expression is tightly regulated by cell-cell adhesion via the E-cadherin-catenin complex and actin cytoskeleton formation.
Akama
Ryota
R
Division of Regulatory Glycobiology, Tohoku Pharmaceutical University, Sendai, Japan.
Sato
Yuya
Y
Kariya
Yoshinobu
Y
Isaji
Tomoya
T
Fukuda
Tomohiko
T
Lu
Lianghao
L
Taniguchi
Naoyuki
N
Ozawa
Masayuki
M
Gu
Jianguo
J
D000199:Actins / Q000235:genetics / Q000378:metabolism*; D019921:Biotinylation; D015153:Blotting, Western; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002240:Carbohydrate Sequence; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D015638:Cytochalasin D / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D047468:Immunoprecipitation; D008858:Microscopy, Phase-Contrast; D008954:Models, Biological; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D051178:alpha Catenin / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D015820:Cadherins; D051178:alpha Catenin; D015638:Cytochalasin D; D017351:N-Acetylglucosaminyltransferases; C054599:beta-1,4-mannosyl-glycoprotein beta-1,4-N-acetylglucosaminyltransferase