Experimental approaches to interfere with the polysialylation of the neural cell adhesion molecule in vitro and in vivo.

Abstract

Sialic acid (Sia) is expressed as terminal sugar in many glycoconjugates and plays an important role during development and regeneration. Addition of homopolymers of Sia (polysialic acid; polySia/PSA) is a unique and highly regulated post-translational modification of the neural cell adhesion molecule (NCAM). The presence of polySia affects NCAM-dependent cell adhesion and plays an important role during brain development, neural regeneration, and plastic processes including learning and memory. PolySia-NCAM is expressed on several neuroendocrine tumors of high malignancy and correlates with poor prognosis. Two closely related enzymes, the polysialyltransferases ST8SiaII and ST8SiaIV, catalyze the biosynthesis of polySia. This review summarizes recent knowledge on Sia biosynthesis and the correlation between Sia biosynthesis and polysialylation of NCAM and report on approaches to modify the degree of polySia on NCAM in vitro and in vivo. First, we describe the inhibition of polysialylation of NCAM in ST8SiaII-expressing cells using synthetic Sia precursors. Second, we demonstrate that the key enzyme of the Sia biosynthesis (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase) regulates and limits the synthesis of polySia by controlling the cellular Sia concentration.

• Authors: Kaya Bork, Daniel Gagiannis, André Orthmann, Wenke Weidemann, Maria Kontou, Werner Reutter, Rüdiger Horstkorte
• Journal: Journal of neurochemistry (J Neurochem) Vol. 103 Suppl 1 Pg. 65-71 (Nov 2007) ISSN: 1471-4159 [Electronic] England
• PMID: 17986141 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Neural Cell Adhesion Molecules
• Sialic Acids
• polysialic acid

Topics

• Animals
• Cell Adhesion (physiology)
• In Vitro Techniques
• Neural Cell Adhesion Molecules (physiology)
• Sialic Acids (biosynthesis, classification, metabolism)