Abstract
Tenascin-R (TN-R) is a member of the tenascin family of multidomain matrix glycoproteins that is expressed exclusively in the central nervous system by oligodendrocytes and small neurons during postnatal development and in the adult. TN-R contributes to the regulation of axon extension and regeneration, neurite formation and synaptogenesis, and neuronal growth and migration. TN-R can be modified with three distinct sulfated oligosaccharide structures: HNK-1 (SO(4)-3-GlcUAbeta1,3Galbeta1,4GlcNAc), GalNAc-4-SO(4), and chondroitin sulfate. We have determined that TN-R expressed in dendrite-rich regions of the rat cerebellum, hippocampus, and cerebral cortex is one of the major matrix glycoproteins that bears N-linked carbohydrates terminating with beta1,4-linked GalNAc-4-SO(4). The syntheses of these unique sulfated structures on TN-R are differentially regulated. Levels of HNK-1 on TN-R rise and fall in parallel to the levels of TN-R during postnatal development of the cerebellum. In contrast, levels of GalNAc-4-SO(4) are regulated independently from those of TN-R, rising late in cerebellar development and continuing into adulthood. As a result, the pattern of TN-R modification with distinct sulfated carbohydrate structures changes dramatically over the course of postnatal cerebellar development in the rat. Because TN-R interacts with a number of different matrix components and, depending on the circumstances, can either activate or inhibit neurite outgrowth, the highly regulated addition of these unique sulfated structures may modulate the adhesive properties of TN-R over the course of development and during synapse maintenance. In addition, the 160-kDa form of TN-R is particularly enriched for terminal GalNAc-4-SO(4) later in development and in the adult, suggesting additional levels of regulation.
Highlights
Neural pattern formation in the central nervous system (CNS)1 involves initial interactions between cell surfaces and components of the extracellular matrix (ECM) that direct cells to proliferate, migrate, and differentiate
TN-R Bears a Major Fraction of the GalNAc-4-SO4 Residues Present in Rat Cerebellum—We previously used a polyclonal goat antibody (anti-TN-R(SC) from Santa Cruz Biotechnology) raised to a synthetic peptide included within the amino-terminal 50 amino acids of TN-R, to identify TN-R as one of the proteins from mouse and rat cerebellum that is bound by immobilized Cys-Fc because it is modified with terminal GalNAc4-SO4 (Fig. 1C) [14]
The same pattern of staining was observed with pTN-R raised to immunopurified mouse TN-R 160 and with monoclonal antibody 596 raised to an HNK-1 positive fraction from chick brain that both react with rat TN-R [11]
Summary
Neural pattern formation in the central nervous system (CNS)1 involves initial interactions between cell surfaces and components of the extracellular matrix (ECM) that direct cells to proliferate, migrate, and differentiate. TN-R Bears a Major Fraction of the GalNAc-4-SO4 Residues Present in Rat Cerebellum—We previously used a polyclonal goat antibody (anti-TN-R(SC) from Santa Cruz Biotechnology) raised to a synthetic peptide included within the amino-terminal 50 amino acids of TN-R, to identify TN-R as one of the proteins from mouse and rat cerebellum that is bound by immobilized Cys-Fc because it is modified with terminal GalNAc4-SO4 (Fig. 1C) [14].
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