Regulated expression and subcellular localization of syndecan heparan sulfate proteoglycans and the syndecan-binding protein CASK/LIN-2 during rat brain development

The syndecan family of cell surface heparan sulfate proteoglycans interacts via their cytoplasmic C-terminal tail with the PDZ domain of CASK/LIN-2, a membrane-associated guanylate kinase homolog. The syndecan-CASK interactio n may be involved in intercellular signaling and/or cell adhesion. Here we show that syndecan-1 to syndecan-4 have distinctive mRNA distributions in a dult rat brain by in situ hybridization, with syndecan-2 and -3 being the m ajor syndecans expressed in neurons of the forebrain. At the protein level, syndecan-2 and -3 are differentially localized within neurons; syndecan-3 is concentrated in axons, whereas syndecan-2 is localized in synapses. The synaptic accumulation of syndecan-2 occurs late in synapse development. CAS K is a cytoplasmic-binding partner for syndecans, and its subcellular distr ibution changes strikingly during development, shifting from a primarily ax onal distribution in the first 2 postnatal weeks to a somatodendritic distr ibution in adult brain. This change in CASK distribution correlates tempora lly and spatially with the expression patterns of syndecan-3 and -2, consis tent with the association of both of these syndecans with CASK in vivo. In support of this, we were able to coimmunoprecipitate a complex of CASK and syndecan-3 from brain extracts. Our results indicate that specific syndecan s are differentially expressed in various cell types of the brain and are t argeted to distinct subcellular compartments in neurons, where they may ser ve specialized functions. Moreover, CASK is appropriately expressed and loc alized to interact with both syndecan-2 and -3 in different compartments of the neuron throughout postnatal development.