DSD-1-Proteoglycan Is the Mouse Homolog of Phosphacan and Displays Opposing Effects on Neurite Outgrowth Dependent on Neuronal Lineage

Abstract

DSD-1-PG is a chondroitin sulfate proteoglycan (CSPG) expressed by glial cells that can promote neurite outgrowth from rat embryonic mesencephalic (E14) and hippocampal (E18) neurons, an activity that is associated with the CS glycosaminoglycans (GAGs). Further characterization of DSD-1-PG has included sequencing of peptides from the core protein and the cloning of the corresponding cDNA using polyclonal antisera against DSD-1-PG to screen phage expression libraries. On the basis of these studies we have identified DSD-1-PG as the mouse homolog of phosphacan, a neural rat CSPG. Monoclonal antibodies 3H1 and 3F8 against carbohydrate residues on rat phosphacan recognize these epitopes on DSD-1-PG. The epitopes of the antibodies, L2/HNK-1 and L5/Lewis-X, which have been implicated in functional interactions, are also found on DSD-1-PG. Although DSD-1-PG has previously been shown to promote neurite outgrowth, its upregulation after stab wounding of the CNS and its localization in regions that are considered boundaries to axonal extension suggested that it may also have inhibitory functions. Neonatal dorsal root ganglion (DRG) explants grown on a rich supportive substrate (laminin) with and without DSD-1-PG were strikingly inhibited by the proteoglycan. The inhibitory effects of DSD-1-PG on the DRG explants were not relieved by removal of the CS GAGs, indicating that this activity is associated with the core glycoprotein. The neurite outgrowth from embryonic hippocampal neurons on laminin was not affected by the addition of DSD-1-PG. This indicates that DSD-1-PG/mouse phosphacan can have opposing effects on the process of neurite outgrowth dependent on neuronal lineage.

Lewis X-carrying N-Glycans Regulate the Proliferation of Mouse Embryonic Neural Stem Cells via the Notch Signaling Pathway

“…It has been reported that NSCs treated with an organic solvent to wash out cell surface glycolipids have strong immunoreactivity with anti-Lewis X antibody (41), indicating that this glycotope is carried mainly by glycoproteins and/or proteoglycans rather than glycolipids. To date, phosphacan, CD24, integrin, L1-CAM, Thy-1, LAMP-1, and TNC have been identified as Lewis X-carrying proteins (36,38,(42)(43)(44)(45). Here, we demonstrated that LAMP-1 and TNC are major Lewis X carriers in NSCs (Fig.…”

Antibodies against the NG2 Proteoglycan Promote the Regeneration of Sensory Axons within the Dorsal Columns of the Spinal Cord

“…and concentrations of different extracellular matrix and cell adhesion molecules can all affect neuronal behavior (Dou and Levine 1995;Snow et al, 1996;Garwood et al, 1999). For example, regenerating axons grow along NG2-positive blood vessels but stop when they contact other types of NG2-expressing cells (Rezajooi et al, 2004).…”

Specific Molecular Interactions of Oversulfated Chondroitin Sulfate E with Various Heparin-binding Growth Factors

“…Maeda et al (20) identified pleiotrophin (PTN), a Hep-binding growthassociated molecule, as a 6B4-PG/phosphacan-binding protein in postnatal day 16 rat brain, and this binding was inhibited by CS-C. 6B4-PG/phosphacan is a major PG in the brain and corresponds to the extracellular region of a receptor-like protein-tyrosine phosphatase, PTP/RPTP␤ (20,21) and recently turned out to be identical with DSD-1-PG (22). MK and PTN constitute a unique family of Hep-binding proteins and share 45% sequence homology at the amino acid level (23,24) in addition to many neuroregulatory activities including promotion of neurite outgrowth (25)(26)(27).…”