Molecular Interactions of Neural Chondroitin Sulfate Proteoglycans in the Brain Development (original) (raw)
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The Journal of cell biology, 1993
Ng-CAM and N-CAM are cell adhesion molecules (CAMs), and each CAM can bind homophilically as demonstrated by the ability of CAM-coated beads (Covaspheres) to self-aggregate. We have found that the extent of aggregation of Covaspheres coated with either Ng-CAM or N-CAM was strongly inhibited by the intact 1D1 and 3F8 chondroitin sulfate proteoglycans of rat brain, and by the core glycoproteins resulting from chondroitinase treatment of the proteoglycans. Much higher concentrations of rat chondrosarcoma chondroitin sulfate proteoglycan (aggrecan) core proteins had no significant effect in these assays. The 1D1 and 3F8 proteoglycans also inhibited binding of neurons to Ng-CAM when mixtures of these proteins were adsorbed to polystyrene dishes. Direct binding of neurons to the proteoglycan core glycoproteins from brain but not from chondrosarcoma was demonstrated using an assay in which cell-substrate contact was initiated by centrifugation, and neuronal binding to the 1D1 proteoglycans...
Journal of Neurobiology, 1998
The expression of proteoglycans ated against IMP. The comparison of PMP and IMP (PGs) in the mammalian central nervous system properties indicates that the two PGs are highly re-(CNS) appears to be strictly regulated both during lated and share expression patterns, biochemical chardevelopment and after damage to the mammalian acteristics, and the ability to inhibit neurite initiation CNS. Recently, we have isolated from membranes of in culture. However, IMP and PMP displayed a disinjured adult brain a neurite outgrowth-inhibitory tinct effect on neurite elongation, which may be exproteoglycan (IMP), the activity of which could be plained by their differences in glycosilation pattern. specifically counteracted by a monoclonal antibody
The Journal of Comparative Neurology, 1996
The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [19941 J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-39421, whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [19921 J. Biol. Chem. 267: 19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4-and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGMl), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents. o 1995 Wiley-Liss, Inc.
Isolation of a neural chondroitin sulfate proteoglycan with neurite outgrowth promoting properties
The Journal of Cell Biology, 1994
Proteoglycans are expressed in various tissues on cell surfaces and in the extracellular matrix and display substantial heterogeneity of both protein and carbohydrate constituents. The functions of individual proteoglycans of the nervous system are not well characterized, partly because specific reagents which would permit their isolation are missing. We report here that the monoclonal antibody 473HD, which binds to the surface of early differentiation stages of murine astrocytes and oligodendrocytes, reacts with the chondroitin sulfate/dermatan sulfate hybrid epitope DSD-1 expressed on a central nervous system chondroitin sulfate proteoglycan designated DSD-1-PG. When purified from detergent-free postnatal days 7 to 14 mouse brain extracts, DSD-1-PG displays an apparent molecular mass between 800-1,000 kD with a prominent core glycoprotein of 350-400 kD. Polyclonal anti-DSD-1-PG antibodies and monoclonal antibody 473HD react with the same molecular species as shown by immunocytochemistry and sequential immunoprecipitation performed on postnatal mouse cerebellar cultures, suggesting that the DSD-1 epitope is restricted to one proteoglycan. DSD-1-PG promotes neurite outgrowth of embryonic day 14 mesencephalic and embryonic day 18 hippocampal neurons from rat, a process which can be blocked by monoclonal antibody 473HD and by enzymatic removal of the DSD-1-epitope. These results show that the hybrid glycosaminoglycan structure DSD-1 supports the morphological differentiation of central nervous system neurons.
Inhibition and enhancement of neural regeneration by chondroitin sulfate proteoglycans
Neural regeneration research, 2017
The current dogma in neural regeneration research implies that chondroitin sulfate proteoglycans (CSPGs) inhibit plasticity and regeneration in the adult central nervous system (CNS). We argue that the role of the CSPGs can be reversed from inhibition to activation by developmentally expressed CSPG-binding factors. Heparin-binding growth-associated molecule (HB-GAM; also designated as pleiotrophin) has been studied as a candidate molecule that might modulate the role of CSPG matrices in plasticity and regeneration. Studies in vitro show that in the presence of soluble HB-GAM chondroitin sulfate (CS) chains of CSPGs display an enhancing effect on neurite outgrowth. Based on the in vitro studies, we suggest a model according to which the HB-GAM/CS complex binds to the neuron surface receptor glypican-2, which induces neurite growth. Furthermore, HB-GAM masks the CS binding sites of the neurite outgrowth inhibiting receptor protein tyrosine phosphatase sigma (PTPσ), which may contribut...
Journal of comparative neurology, 1996
The first thalamocortical axons to arrive in the developing cerebral cortex traverse a pathway that is separate from the adjacent intracortical pathway for early efferents, suggesting that different molecular signals guide their growth. We previously demonstrated that the intracortical pathway for thalamic axons is centered on the subplate (Bicknese et al. [19941 J. Neurosci. 14:3500-3510), which is rich in chondroitin sulfate proteoglycans (CSPGs; Sheppard et al. [1991] J. Neurosci. 11:3928-39421, whereas efferent axons cross the subplate to exit in a zone containing much less CSPG. To define the molecular composition of the subplate further, we used antibodies against CSPG core proteins and chondroitin sulfate disaccharides in an immunohistochemical analysis of their distribution in the developing neocortex of the rat. Immunolabeling for neurocan, a central nervous system-specific CSPG (Rauch et al. [19921 J. Biol. Chem. 267: 19537-19547), and for chondroitin 6-sulfate and unsulfated chondroitin becomes prominent in the subplate before the arrival of thalamic afferents. Immunolabeling is initially sparse in the cortical plate but appears later in maturing cortical layers. A postnatal decline in immunolabeling occurs uniformly for most proteoglycans, but, in the somatosensory cortex, labeling for neurocan, phosphacan, and chondroitin 4-and 6-sulfate declines in the centers of the whisker barrels before the walls. In contrast to neurocan, immunolabeling for other proteoglycans is either uniformly distributed (syndecan-1, N-syndecan, 5F3, phosphacan, chondroitin 4-sulfate), restricted to axons (PGMl), distributed exclusively on nonneuronal elements (2D6, NG2, and CD44), or undetectable (9.2.27, aggrecan, decorin). Thus, neurocan is a candidate molecule for delineating the intracortical pathway of thalamocortical axons and distinguishing it from that of cortical efferents.
Neural precursors express multiple chondroitin sulfate proteoglycans, including the lectican family
Biochemical and Biophysical Research Communications, 2004
Chondroitin sulfate proteoglycans (CSPGs) abnormally accumulate in cerebrospinal fluid (CSF) of both human neonates with preterm hydrocephalus, and P8 hydrocephalic mice. We hypothesized CSF CSPGs are synthesized by neural precursors, separated from ventricular CSF by ependyma, which is often disrupted in hydrocephalus. Western blotting demonstrates that neural precursors cultured as neurospheres secrete CSPGs (>30 lg/ml) into their media which appear to be very similar to these CSF CSPGs. Some CSPGs bear the stage-specific embryonic antigen-1 (ssea-1), associated with embryonic/neural stem cells. Neurospheres transcribe many CSPG genes, including the entire aggrecan/lectican family, phosphacan, and tenascin. Phosphacan can be detected in media by Western blotting. Aggrecan can be detected in media after purification using hyaluronic acid affinity chromatography. During differentiation, neurospheres downregulate CSPGs. This is the first report to show that proliferating neural precursors synthesize lecticans, including aggrecan, which are downregulated with differentiation. These observations suggest novel links between CSPGs and CNS precursor biology.
Proteoglycans in the developing brain: new conceptual insights for old proteins
Physiological reviews, 2000
Proteoglycans are a heterogeneous class of proteins bearing sulfated glycosaminoglycans. Some of the proteoglycans have distinct core protein structures, and others display similarities and thus may be grouped into families such as the syndecans, the glypicans, or the hyalectans (or lecticans). Proteoglycans can be found in almost all tissues being present in the extracellular matrix, on cellular surfaces, or in intracellular granules. In recent years, brain proteoglycans have attracted growing interest due to their highly regulated spatiotemporal expression during nervous system development and maturation. There is increasing evidence that different proteoglycans act as regulators of cell migration, axonal pathfinding, synaptogenesis, and structural plasticity. This review summarizes the most recent data on structures and functions of brain proteoglycans and focuses on new physiological concepts for their potential roles in the developing central nervous system.
Journal of Biological Chemistry, 2006
Neuroglycan C (NGC) is a transmembrane-type chondroitin sulfate proteoglycan that is exclusively expressed in the central nervous system. We report that the recombinant ectodomain of NGC core protein enhances neurite outgrowth from rat neocortical neurons in culture. Both protein kinase C (PKC) inhibitors and phosphatidylinositol 3-kinase (PI3K) inhibitors attenuated the NGC-mediated neurite outgrowth in a dose-dependent manner, suggesting that NGC promotes neurite outgrowth via PI3K and PKC pathways. The active sites of NGC for neurite outgrowth existed in the epidermal growth factor (EGF)-like domain and acidic amino acid (AA)-domain of the NGC ectodomain. The EGF-domain caused cells to extend preferentially one neurite from a soma, whereas the AA-domain caused several neurites to develop. The EGF-domain also enhanced neurite outgrowth from GABA-positive neurons, but the AA-domain did not. These results suggest that the EGF-domain and AA-domain have distinct functions in terms of neuritogenesis. From these findings, NGC can be considered to be involved in neuritogenesis in the developing central nervous system. Proteoglycans (PGs) 3 are a group of proteins with covalently attached sulfated glycosaminoglycan (GAG) chains. In the cen-* This work was supported in part by grants-in-aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan, and from the Japan Society for the Promotion of Science. The costs of publication of this article were defrayed in part by the payment of page charges.