Spatial and Temporal Regulation of Tenascin-R Glycosylation in the Cerebellum

Abstract

The cellular adhesion molecule tenascin-R is a multifunctional extracellular matrix component expressed exclusively in the central nervous system. The expression of tenascin-R by oligodendrocytes and small interneurons in the hippocampus and cerebellum is highly regulated during development of these regions. This complex glycoprotein displays both adhesive and antiadhesive properties that contribute to the formation and maintenance of synapses. We have determined that tenascin-R associated with Purkinje cell bodies and their dendrites in the molecular layer of the cerebellum bears N-linked oligosaccharides terminating with ␤1,4-linked GalNAc-4-SO 4 , whereas tenascin-R in other regions of the cerebellum does not bear this modification. Expression of this unique sulfated carbohydrate structure is also temporally regulated, increasing throughout cerebellar development. The most dramatic increase in GalNAc-4-SO 4 occurs between postnatal days 14 and 21, corresponding to a period of Purkinje cell dendrite extension and synaptogenesis. The spatially and temporally regulated addition of this unique sulfated carbohydrate to tenascin-R may serve to modulate its adhesive/anti-adhesive or other biological properties in vivo.

N-Linked Oligosaccharides on the Low Density Lipoprotein Receptor Homolog SorLA/LR11 Are Modified with Terminal GalNAc-4-SO4 in Kidney and Brain

“…Furthermore, GalNAc-4-sulfotransferase and protein-specific ␤1,4GalNAc-transferase activities are also expressed in the brain (27), and Cys-Fc reactive material is particularly prominent in the cerebellum and hippocampus (15,16). We recently reported that the extracellular matrix protein tenascin-R is modified with terminal GalNAc-4-SO 4 and can be bound to immobilized Cys-Fc (15).…”

“…Because the Cys-rich domain of the Man/GalNAc-4-SO 4 receptor is highly specific for terminal sulfated sugars such as ␤1,4-linked GalNAc-4-SO 4 (25,28,29), we utilized a chimeric protein consisting of the Cys-rich domain and the Fc domain of human IgG, Cys-Fc, to immunostain tissue sections for the presence of glycoproteins bearing terminal ␤1,4-linked GalNAc-4-SO 4 (15,25). Cells comprising collecting ducts in the medulla and papilla of the mouse kidney are intensely stained (Fig.…”

“…The cysteine-rich domain, a region located near the amino terminus of the mannose/GalNAc-4-SO 4 -receptor, accounts for GalNAc-4-SO 4 binding (25). We have used a chimeric protein termed Cys-Fc, which consists of the cysteinerich domain and the constant region of human IgG1, to identify tissues and specific cells that express glycoproteins bearing terminal GalNAc-4-SO 4 and to isolate these glycoproteins by affinity chromatography (15,16,25). In this report we provide evidence that SorLA/LR11 is among the small family of glycoproteins that are modified with N-linked oligosaccharides that terminate with ␤1,4-linked GalNAc-4-SO 4 .…”

Ablation of GalNAc-4-sulfotransferase-1 enhances reproduction by altering the carbohydrate structures of luteinizing hormone in mice

“…There are a number of glycoproteins synthesized in other tissues that are also selectively modified with terminal GalNAc-4-SO 4 , for example, the LDL-receptor homolog SorLA/LR11 expressed in the kidney and the brain (48) and tenascin-R expressed in the brain (49). It is possible that additional differences between WT and GalNAc-4-ST1 -/-mice will be identified upon further examination; however, none of the other glycoproteins identified thus far as bearing structures terminating with SO 4 -4-GalNAcβ1,4GlcNAc would be expected to have an impact on steroid hormone production or reproduction.…”

Novel Poly-GalNAcβ1–4GlcNAc (LacdiNAc) and Fucosylated Poly-LacdiNAc N-Glycans from Mammalian Cells Expressing β1,4-N-Acetylgalactosaminyltransferase and α1,3-Fucosyltransferase

“…However, another type of nonreducing terminal glycan structure that is less well understood but now appears to also be expressed by many organisms, including mammals, is based on the LacdiNAc (LDN) sequence GalNAc␤1-4GlcNAc-R, which can also occur within 4-O-sulfated, ␣1,3-fucosylated, or ␣2,6-sialylated derivatives. LDN-type glycans play vital roles in regulating the circulatory half-life of pituitary glycoprotein hormones (1-3) and other glycoproteins (4,5), including tenascin-R produced by oligodendrocytes and small interneurons in the hippocampus and cerebellum (6). Other glycoproteins containing LDN-type glycans include human glycodelin, a human glycoprotein with potent immunosuppressive and contraceptive activities (7,8), and zona pellucida glycoproteins from murine eggs (9).…”