The polysialyltransferases interact with sequences in two domains of the neural cell adhesion molecule to allow its polysialylation
journal contributionposted on 2014-04-15, 00:00 authored by Matthew G. Thompson, Deirdre A. Foley, Karen J. Colley
The neural cell adhesion molecule, NCAM, is the major substrate for the polysialyltransferases (polySTs), ST8SiaII/STX and ST8SiaIV/PST. The polysialylation of NCAM N-glycans decreases cell adhesion and alters signaling. Previous work demonstrated that the first fibronectin type III repeat (FN1) of NCAM is required for polyST recognition and the polysialylation of the N-glycans on the adjacent Ig5 domain. In this work we highlight the importance of an FN1 acidic patch in polyST recognition, and also reveal that the polySTs are required to interact with sequences in the Ig5 domain for polysialylation to occur. We find that features of the Ig5 domain of the olfactory cell adhesion molecule, OCAM, are responsible for its lack of polysialylation. Specifically, two basic OCAM Ig5 residues (Lys, Arg) found near asparagines equivalent to those carrying the polysialylated N-glycans in NCAM, substantially decrease or eliminate polysialylation when used to replace the smaller and more neutral residues (Ser, Asn) in analogous positions in NCAM Ig5. This decrease in polysialylation does not reflect altered glycosylation, but instead is correlated with a decrease in polyST-NCAM binding. In addition, inserting non-conserved OCAM sequences into NCAM Ig5, including an extra N-glycosylation site, decreases or completely blocks NCAM polysialylation. Taken together, these results indicate that the polySTs not only recognize an acidic patch in the FN1 domain of NCAM, but also must contact sequences in the Ig5 domain for polysialylation of Ig5 N-glycans to occur.
This work was supported by NIH grants RO1 GM63843 to KJC
Publisher StatementThis research was originally published in Journal of Biological Chemistry. Thompson MG, Foley DA, Colley KJ. The polysialyltransferases interact with sequences in two domains of the neural cell adhesion molecule to allow its polysialylation. Journal of Biological Chemistry. 2013 Jan 22. © the American Society for Biochemistry and Molecular Biology
CitationThompson MG, Foley DA, Colley KJ. The polysialyltransferases interact with sequences in two domains of the neural cell adhesion molecule to allow its polysialylation.Journal of Biological Chemistry. Jan 22 2013. doi: 10.1074/jbc.M112.438374
PublisherAmerican Society for Biochemistry and Molecular Biology