Abstract
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).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
