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The Biosynthesis of Polysialic Acid: A Developmentally Regulated, Anti‐Adhesive Glycan
Author(s) -
Colley Karen Jane,
Thompson Matthew G,
Foley Deirdre A,
Zapater Joseph L
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.349.1
Subject(s) - polysialic acid , glycan , neural cell adhesion molecule , chemistry , sialic acid , biochemistry , glycoprotein , enzyme , cell , cell adhesion
Polysialic acid is a unique glycan that modulates cell adhesion and signaling, and is critical for brain development, neuronal regeneration, and cancer invasiveness. Polysialic acid is found on a limited number of glycoproteins suggesting that polysialylation is a protein‐specific modification that requires an initial polysialyltransferase (polyST)‐substrate protein‐protein interaction. Previously we found that acidic residues on the surface of the first fibronectin type III repeat of NCAM are required for the polysialylation of the N‐glycans on its adjacent immunoglobulin domain. Using competition and polysialylation assays we have identified a polyST polybasic region that is involved in substrate recognition. Truncated, catalytically inactive ST8Sia IV (PST) proteins containing this region are effective inhibitors of NCAM polysialylation. Replacing Arg82 and Arg93 in region substantially decreases NCAM polysialylation by PST without equally compromising enzyme activity, and also eliminates the ability of a catalytically inactive PST mutant (H331K) to block NCAM polysialylation. In contrast, replacing only Arg82 eliminates the ability of PST to polysialylate SynCAM 1 and neuropilin‐2. These results suggest that the polySTs may use distinct but overlapping basic sites to recognize different substrates. Supported by NIH RO1 GM063843 (KJC) and NIH F31 GM096739 (JLZ).