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. 2003 Dec 5;278(49):49459-68.
doi: 10.1074/jbc.M308316200. Epub 2003 Sep 17.

Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion

Misa Suzuki  1 , Kiyohiko Angata, Jun Nakayama, Minoru Fukuda
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Free article

Polysialic acid and mucin type o-glycans on the neural cell adhesion molecule differentially regulate myoblast fusion

Misa Suzuki et al. J Biol Chem. .
Free article

Abstract

Polysialic acid attached to the neural cell adhesion molecule (NCAM) is thought to play a critical role in development. NCAM in muscle tissue contains a muscle-specific domain (MSD) to which mucin type O-glycans are attached. In the present study, using the C2C12 myoblast system, we show that NCAM containing MSD is increasingly expressed on the cell surface as myotubes form. Polysialic acid is primarily attached to N-glycans of NCAM, and polysialylated NCAM is expressed on the outer surface of myotube bundles. By transfecting cDNAs encoding wild type and mutant forms of NCAM, we found that NCAM containing MSD facilitates myoblast fusion, and this effect is diminished by mutating O-glycosylation sites at MSD. By contrast, forced expression of polysialic acid in early differentiation stages reduces myotube formation and delays the expression of NCAM containing the MSD domain. Strikingly, inhibition of polysialic acid synthesis by antisense DNA approach induced differentiation in both human rhabdomyosarcoma cells, which overexpress polysialic acid, and C2C12 cells. These results indicate that polysialic acid and mucin type O-glycans on NCAM differentially regulate myoblast fusion, playing critical roles in muscle development.

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