Polysialic acid in brain development and synaptic plasticity

Abstract

Polymers of sialic acid can be produced by pro- and eukaryotic cells. In vertebrates polysialic acid consists of α2,8-linked N-acetylneuraminic acid and is most prominent during nervous system development. Polysialic acid is produced by two complementary sialyltransferases, ST8SiaII and ST8SiaIV. The major, but not the only, carrier of polysialic acid is the neural cell adhesion molecule (NCAM). In this review we highlight how polySia dictates the interactions of various cell types during development and plasticity of the vertebrate central nervous system on different molecular levels. Recent progress in generating mouse models with differential ablation of the polysialyltransferases or NCAM revealed the dramatic impact of polysialic acid-negative NCAM on brain development and elaborate electrophysiological studies allowed for new insights into the role of polysialic acid in regulating synaptic plasticity and learning. The implications of dysregulated polysialylation for brain disease and neuropsychiatric disorders are discussed.