Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Neurocan”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 91 records · Page 5Linked to original sources
PubMed2004

Developmental changes in the biochemical and immunological characters of the carbohydrate moiety of neuroglycan C, a brain-specific chondroitin sulfate proteoglycan.

Neuroglycan C (NGC), a brain-specific transmembrane proteoglycan, is thought to bear not only chondroitin sulfate but also N- and O-linked oligosaccharides on its core protein. In this study, we isolated and purified NGC from rat brains at various developmental stages by immunoaffinity column chromatography or by immunoprecipitation, and examined the structural characters of its carbohydrate moiety. The chondroitin sulfate disaccharide composition of NGC at postnatal day 10 was significantly different from those of two secreted chondroitin sulfate proteoglycans, neurocan and phosphacan, purified from the brain at the same developmental stage; higher levels of 4-sulfate unit and E unit, a disulfated disaccharide unit, and a lower level of 6-sulfate unit. The levels of both 6-sulfate and E units decreased with a compensatory increase of 4-sulfate unit with postnatal development of the brain. Lectin-blot analysis of the NGC core glycoprotein prepared by chondroitinase digestion confirmed that NGC actually bore both N- and O-linked carbohydrates, and also revealed that lectin-species reactive with NGC did not always recognize other brain-specific proteoglycans, neurocan and phosphacan, and vice versa, even though they were isolated from the brain at the same stage. The reactivity of NGC with lectins and with the HNK-1 antibody markedly changed as the brain matured. These findings indicate that the structure of the carbohydrate moiety of NGC is developmentally regulated, and differs from those of neurocan and phosphacan. The developmentally-regulated structural change of the carbohydrates on NGC may be partly implicated in the modulation of neuronal cell recognition during brain development.

Aging↗
PubMed1999

Fibulin-1 is a ligand for the C-type lectin domains of aggrecan and versican.

The aggregating proteoglycans (aggrecan, versican, neurocan, and brevican) are important components of many extracellular matrices. Their N-terminal globular domain binds to hyaluronan, but the function of their C-terminal region containing a C-type lectin domain is less clear. We now report that a 90-kDa protein copurifies with recombinant lectin domains from aggrecan and versican, but not from the brain-specific neurocan and brevican. Amino acid sequencing of tryptic peptides from this protein identified it as fibulin-1. This extracellular matrix glycoprotein is strongly expressed in tissues where versican is expressed (blood vessels, skin, and developing heart), and also expressed in developing cartilage and bone. It is thus likely to interact with these proteoglycans in vivo. Surface plasmon resonance measurements confirmed that aggrecan and versican lectin domains bind fibulin-1, whereas brevican and neurocan do not. As expected for a C-type lectin, the interactions with fibulin-1 are Ca2+-dependent, with KD values in the low nanomolar range. Using various deletion mutants, the binding site for aggrecan and versican lectin domains was mapped to the epidermal growth factor-like repeats in domain II of fibulin-1. No difference in affinity was found for deglycosylated fibulin-1, indicating that the proteoglycan C-type lectin domains bind to the protein part of fibulin-1.

Aggrecans↗
PubMed1993

Functional characterization of chondroitin sulfate proteoglycans of brain: interactions with neurons and neural cell adhesion molecules.

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 was specifically inhibited by the 1D1 monoclonal antibody. Different forms of the 1D1 proteoglycan have been identified in developing and adult brain. The early postnatal form (neurocan) was found to bind neurons more effectively than the adult proteoglycan, which represents the C-terminal half of the larger neurocan core protein. Our results therefore indicate that certain brain proteoglycans can bind to neurons, and that Ng-CAM and N-CAM may be heterophilic ligands for neurocan and the 3F8 proteoglycan. The ability of these brain proteoglycans to inhibit adhesion of cells to CAMs may be one mechanism to modulate cell adhesion and migration in the nervous system.

Aging↗
PubMed2002

Proteoglycans in the eye.

PURPOSE: Various proteoglycans are expressed in ocular tissues. We investigated and reviewed the distribution and the potential roles of proteoglycans in cornea, trabecular meshwork, and retinal tissues. METHODS: Immunohistochemical studies were performed in rat ocular tissues. The concentration of transforming growth factor (TGF)-beta2, which regulates the expression of proteoglycans in aqueous humor from human glaucomatous eyes, was evaluated by enzyme-linked immunosorbent assay (ELISA). In retinal tissues, we examined the localization of 2 soluble nervous tissue-specific chondroitin sulfate proteoglycans, neurocan and phosphacan, by immunohistochemical analysis, then investigated the effect on the neurite outgrowth of cultivated retinal ganglion cells. RESULTS: The expression of chondroitin sulfate in stroma was upregulated at early postnatal stages and reduced during development in rat eyes. In trabecular meshwork tissues, immunohistochemical studies showed the intense expression of decorin. Moreover, elevated levels of TGF-beta2 in the aqueous humor from glaucomatous patients were observed. In retinal tissues, neurocan and phosphacan were expressed mainly in nerve fiber-rich layers during rat postnatal stages. In vitro, the neurite extension from retinal ganglion cells was inhibited by neurocan and phosphacan. CONCLUSIONS: Soluble extracellular proteoglycans in corneal and trabecular meshwork tissues contribute to the stromal transparency in the corneal tissues and the resistance of the aqueous humor outflow in trabecular meshwork tissues. In retinal tissues, chondroitin sulfate and heparan sulfate proteoglycans are not only secreted into the extracellular space of retinal tissues but also expressed in the membrane of the retinal cells, contributing to the neural network formation and the maintenance of the interphotoreceptor matrix.

Animals↗
PubMed1995

[Proteoglycans in the developing brain].

The occurrence of multiple proteoglycan species is a characteristic of the brain. To identify each proteoglycan molecule, we have raised several monoclonal antibodies against either the soluble or membrane-bound proteoglycan fraction from 10-day-old rat brains. The monoclonal antibody 1G2 recognized neurocan, a soluble chondroitin sulfate proteoglycan (CSPG) unique to the brain. Immunohistological and cell biological results suggested that neurocan regulates neurite outgrowth through specific binding to N-CAM and Ng-CAM at the surface of neurons. In addition, the expression of neurocan was dependent upon neuronal activity evoked by environmental stimuli at least in the developing barrel field. Another CSPG, 6B4-PG, was expressed specifically in the cerebellar mossy fiber system in the rat hindbrain, suggesting that it plays roles in the establishment of this particular neuronal circuit. A membrane-bound heparan sulfate proteoglycan with a 140 kDa core glycoprotein (tentatively designated growth-can) was shown immunohistologically to be transiently expressed in association with growing axons and at the sites of synapse formation. Thus, many neuronal proteoglycans may be involved in various phases of neuronal network formation in the brain. In the near future, progress both in molecular cloning of core proteins and in glycobiology of carbohydrates of proteoglycans will probably produce much experimental evidence to show that neural proteoglycans play pivotal roles during various stages of brain development.

Animals↗
PubMed2000

Chondroitin sulfate proteoglycan expression pattern in hippocampal development: potential regulation of axon tract formation.

A variety of molecular influences in the extracellular matrix (ECM) interact with developing axons to guide the formation of hippocampal axon pathways. One of these influences may be chondroitin sulfate proteoglycans (CSPGs), which are known to inhibit axonal extension during development and following central nervous system injury. In this study, we examined the role of CSPGs and cell adhesion molecules in the regulation of axon tract formation during hippocampal development. We used indirect immunofluorescence to examine the developmental pattern of CSPG expression relative to axon tracts that express the cell adhesion molecule L1. Additionally, we used dissociated and explant cell cultures to examine the effects of CSPGs on hippocampal axon development in vitro. In vivo, we found that the CSPG neurocan is expressed throughout the alveus, neuropil layers, and parts of the dentate gyrus from E16 to P2. The CSPG phosphacan is expressed primarily in the neuropil layers at postnatal stages. After E18, intense labeling of neurocan was observed in regions of the alveus surrounding L1-expressing axon fascicles. In vitro, axons from brain regions that project through the alveus during development would not grow across CSPG substrata, in a concentration-dependent manner. In addition, hippocampal axons from dissociated neuron cultures only traveled across CSPG substrata as fasciculated axon bundles. These findings implicate CSPG in the regulation of axon trajectory and fasciculation during hippocampal axon tract formation.

Animals↗
PubMed2005

Growth factor and cytokine regulation of chondroitin sulfate proteoglycans by astrocytes.

After injury to the adult central nervous system (CNS), numerous cytokines and growth factors are released that contribute to reactive gliosis and extracellular matrix production. In vitro examination of these cytokines revealed that the presence of transforming growth factor-beta1 (TGF-beta1) and epidermal growth factor (EGF) greatly increased the production of several chondroitin sulfate proteoglycans (CSPG) by astrocytes. Treatment of astrocytes with other EGF-receptor (ErbB1) ligands, such as TGF-alpha and HB-EGF, produced increases in CSPG production similar to those observed with EGF. Treatment of astrocytes, however, with heregulin, which signals through other members of the EGF-receptor family (ErbB2, ErbB3, ErbB4), did not induce CSPG upregulation. The specificity of activation through the ErbB1 receptor was further verified by using a selective antagonist (AG1478) to this tyrosine kinase receptor. Western blot analysis of astrocyte supernatant pre-digested with chondroitinase ABC indicated the presence of multiple core proteins containing 4-sulfated or 6-sulfated chondroitin. To identify some of these CSPGs, Western blots were screened using antibodies to several known CSPG core proteins. These analyses showed that treatment of astrocytes with EGF increased phosphacan expression, whereas treatment with TGF-beta1 increased neurocan expression. Reverse transcription-polymerase chain reaction (RT-PCR) was used to examine the expression of these molecules in vivo, which result in increased expression of TGF-beta1, EGF-receptor, neurocan, and phosphacan after injury to the brain. These data begin to elucidate some of the injury-induced growth factors that regulate the expression of CSPGs which could be targeted in the future to modulate CSPG production after injury to the central nervous system.

Animals↗
PubMed2004

Extracellular matrix components associated with remodeling processes in brain.

In the central nervous system, various extracellular matrix components have been identified which are strongly expressed during development and in most areas of the brain down-regulated during maturation. Examples are tenascin-C, neurocan and hyaluronan. While tenascin-C is well known to be associated with morphogenic events and the active contribution of hyaluronan to various physiological processes is increasingly acknowledged, neurocan belongs to a class of molecules thought to be generally more associated with barrier functions: chondroitin sulfate proteoglycans. Consideration of these and related molecules and their processing in the context of the general organization of the brain extracellular matrix, their changes during brain maturation and their implication in different types of remodeling processes in adult brain, like normal and pathological synaptic plasticity, inflammatory and dementia-associated diseases and gliomas, may indicate that components of the extracellular matrix could provide valuable early information about the pathological state of the brain.

Brain↗
PubMed2005

Extracellular matrix alterations in brains lacking four of its components.

The organization of the brain extracellular matrix appears to be based on aggregates of hyaluronan and proteoglycans, connected by oligomeric glycoproteins. Mild phenotypical consequences were reported from several mouse strains lacking components of this matrix such as neurocan, brevican, tenascin-R, and tenascin-C. To further challenge the flexibility of the extracellular matrix network of the brain, mice lacking all four brain extracellular matrix molecules were generated, which were found to be viable and fertile. Analysis of the brains of 1-month-old quadruple KO mice revealed increased protein levels of fibulin-1 and fibulin-2. Histochemical analysis showed an unusual parenchymal deposition of these fibulins. The quadruple KO mice also displayed obvious changes in the pattern of deposition of hyaluronan. Further, an almost quadruple knockout like extracellular environment was noticed in the brains of triple knockout mice lacking both tenascins and brevican, since these brains had strongly reduced levels of neurocan.

Animals↗
PubMed2006

Composition of perineuronal net extracellular matrix in rat brain: a different disaccharide composition for the net-associated proteoglycans.

We developed a method to extract differentially chondroitin sulfate proteoglycans (CSPGs) that are diffusely present in the central nervous system (CNS) matrix and CSPGs that are present in the condensed matrix of perineuronal nets (PNNs). Adult rat brain was sequentially extracted with Tris-buffered saline (TBS), TBS-containing detergent, 1 m NaCl, and 6 m urea. Extracting tissue sections with these buffers showed that the diffuse and membrane-bound CSPGs were extracted in the first three buffers, but PNN-associated CSPGs remained and were only removed by 6 m urea. Most of the CSPGs were extracted to some degree with all the buffers, with neurocan, brevican, aggrecan, and versican particularly associated with the stable urea-extractable PNNs. The CSPGs in stable complexes only extractable in urea buffer are found from postnatal day 7-14 coinciding with PNN formation. Disaccharide composition analysis indicated a different glycosaminoglycan (GAG) composition for PGs strongly associated with extracellular matrix (ECM). For CS/dermatan sulfate (DS)-GAG the content of nonsulfated, 6-O-sulfated, 2,6-O-disulfated, and 4,6-O-disulfated disaccharides were higher and for heparan sulfate (HS)-GAG, the content of 6-O-sulfated, 2-N-, 6-O-disulfated, 2-O-, 2-N-disulfated, and 2-O-, 2-N-, 6-O-trisulfated disaccharides were higher in urea extract compared with other buffer extracts. Digestions with chondroitinase ABC and hyaluronidase indicated that aggrecan, versican, neurocan, brevican, and phosphacan are retained in PNNs through binding to hyaluronan (HA). A comparison of the brain and spinal cord ECM with respect to CSPGs indicated that the PNNs in both parts of the CNS have the same composition.

Age Factors↗
PubMed2004

Differential upregulation of extracellular matrix molecules associated with the appearance of granule cell dispersion and mossy fiber sprouting during epileptogenesis in a murine model of temporal lobe epilepsy.

We have investigated changes in the extracellular matrix of the hippocampus associated with the early progression of epileptogenesis in a murine model of temporal lobe epilepsy using immunohistochemistry. In the first week following intrahippocampal injection of the glutamate agonist, domoate, there is a latent period at the end of which begins a sequential upregulation of extracellular matrix (ECM) molecules in the granule cell layer of the dentate gyrus, beginning with neurocan and tenascin-C. This expression precedes the characteristic dispersion of the granule cell layer which is evident at 14 days post-injection when the first recurrent seizures can be recorded. At this stage, an upregulation of the chondroitin sulfate proteoglycan, phosphacan, the DSD-1 chondroitin sulfate motif, and the HNK-1 oligosaccharide are also observed. The expression of these molecules is localized differentially in the epileptogenic dentate gyrus, especially in the sprouting molecular layer, where a strong upregulation of phosphacan, tenascin-C, and HNK-1 is observed but there is no expression of the proteoglycan, neurocan, nor of the DSD-1 chondroitin sulfate motif. Hence, it appears that granule cell layer dispersion is accompanied by a general increase in the ECM, while mossy fiber sprouting in the molecular layer is associated with a more restricted repertoire. In contrast to these changes, the expression of the ECM glycoproteins, laminin and fibronectin, both of which are frequently implicated in tissue remodelling events, showed no changes associated with either granule cell dispersion or mossy fiber sprouting, indicating that the epileptogenic plasticity of the hippocampus is accompanied by ECM interactions that are characteristic of the CNS.

Animals↗
PubMed2003

Region and lamina-specific distribution of extracellular matrix proteoglycans, hyaluronan and tenascin-R in the mouse hippocampal formation.

The extracellular matrix is known to show region-specific characteristics in the adult brain. Our comparative cytochemical study is focused on the laminar organisation of major extracellular matrix constituents in the murine hippocampal formation, including the regions CA1, CA2 and CA3 of the hippocampus proper, the dentate gyrus, the subiculum and the presubiculum. Components related to chondroitin sulphate proteoglycans were detected by N-acetylgalactosamine-binding Wisteria floribunda agglutinin, colloidal iron staining, and antibodies to different proteoglycan domains, including the Cat-301 and Cat-315 epitopes of aggrecan, as well as neurocan, brevican and phosphacan. The distribution patterns of these components were correlated with the patterns revealed for hyaluronan and the brain-specific extracellular matrix glycoprotein, tenascin-R, known to be ligands of extracellular matrix proteoglycans. Lectin binding clearly labelled perineuronal nets of the extracellular matrix around interneurons, which were preferentially located within or near the principal cell layers in all regions. In the hippocampus proper, the CA2 subfield showed an intense labelling of the neuropil around pyramidal cell bodies and the neuropil zones in the strata oriens and radiatum. These patterns were also seen after immunoreaction for chondroitin proteoglycan domains, brevican and phosphacan, as well as after detection of hyaluronan and tenascin-R. Characteristic laminar and intralaminar patterns were additionally expressed in the neuropil in all regions. In the dentate gyrus, the staining intensity for brevican, phosphacan and tenascin-R was predominant in the middle molecular layer, and for Cat-315 in the inner molecular layer, whereas immunoreactivity for neurocan increased within the outer molecular layer towards the hippocampal fissure. Our findings indicate that proteoglycans, hyaluronan and tenascin-R show differential patterns of co-expression in the individual regions and laminae of the hippocampal formation. The inhomogeneous composition of these major components suggests that the extracellular matrix is specifically adapted to the functional domains of intrahippocampal connections and afferent fibre systems.

Animals↗
PubMed2001

The proteoglycans aggrecan and Versican form networks with fibulin-2 through their lectin domain binding.

Aggrecan, versican, neurocan, and brevican are important components of the extracellular matrix in various tissues. Their amino-terminal globular domains bind to hyaluronan, but the function of their carboxyl-terminal globular domains has long remained elusive. A picture is now emerging where the C-type lectin motif of this domain mediates binding to other extracellular matrix proteins. We here demonstrate that aggrecan, versican, and brevican lectin domains bind fibulin-2, whereas neurocan does not. As expected for a C-type lectin, the interactions are calcium-dependent, with K(D) values in the nanomolar range as measured by surface plasmon resonance. Solid phase competition assays with previously identified ligands demonstrated that fibulin-2 and tenascin-R bind the same site on the proteoglycan lectin domains. Fibulin-1 has affinity for the common site on versican but may bind to a different site on the aggrecan lectin domain. By using deletion mutants, the interaction sites for aggrecan and versican lectin domains were mapped to epidermal growth factor-like repeats in domain II of fibulin-2. Affinity chromatography and solid phase assays confirmed that also native full-length aggrecan and versican bind the lectin domain ligands. Electron microscopy confirmed the mapping and demonstrated that hyaluronan-aggrecan complexes can be cross-linked by the fibulins.

Aggrecans↗
PubMed2001

Immunohistochemical localization of large chondroitin sulphate proteoglycan in porcine gingival epithelia.

In this study, we report the immunohistochemical localization of versican in healthy porcine gingival epithelia. The monoclonal antibody (mAb), 5D5, specifically recognizes core proteins of large chondroitin sulphate proteoglycans such as versican, neurocan and brevican, but not the core protein of aggrecan. Because neurocan and brevican appear to be specific to nervous tissue, the large chondroitin sulphate proteoglycans examined in this study is most likely versican. In the keratinized layer of the attached gingival epithelium, the basal and spinous cell surfaces showed intense staining for mAb 5D5. In the parakeratinized layer of the sulcus epithelium, the localization was restricted to the basal and lower spinous layers. In the junctional epithelium, intense staining was observed in one or two cell layers near the enamel surface. Immunoelectron microscopy revealed high-density depositions of 5D5 immunoreactivity on epithelial cell surfaces. At the enamel surface, 5D5 immunoreactivity was localized to the dental cuticle of the junctional epithelium but was not present in the internal basal lamina. These results suggest that versican, a large chondroitin sulphate proteoglycan, is involved in epithelial differentiation and downgrowth.

Animals↗
PubMed1995

Chondroitin sulphate proteoglycans in the rat brain: candidates for axon barriers of sensory neurons and the possible modification by laminin of their actions.

The addition of chondroitin sulphate proteoglycans (CSPGs), purified from the rat brain, to the culture medium of PC12D cells inhibited their proliferation and neurite outgrowth. Therefore, we investigated the effects of several extracellular components on the inhibitory actions of CSPGs on PC12D cells, as well as their immunocytochemical distribution in the rat embryo to determine whether the findings in vitro could be reproduced in vivo. Coating of the substratum with polylysine was necessary for the appearance of the inhibitory effects of brain CSPGs on PC12D cells. The additional pretreatment of polylysine-coated dishes with laminin or fibronectin promoted the outgrowth of neurites from PC12D cells. Laminin and fibronectin, but not collagen (types I and IV) and CELL-TAK (cell adhesion molecules), prevented the inhibitory effects of brain CSPGs in a concentration-dependent manner. Doses producing 50% reduction by laminin (or fibronectin) of the CSPG effects were 1.5 (or 25) micrograms/ml for neurite outgrowth and 2.2 (or 28) micrograms/ml for proliferation. The ratio of dish-attached CSPGs to laminin necessary for 50% reduction was about approximately 50:1 (wt/wt). Laminin from any source had the same effect. Brain CSPGs also obviously impeded the growth of fibres from dorsal root ganglion explants and primary cultured dorsal root ganglion neurons. Neurocan (a major CSPG in the brain)-like immunoreactivity was detected in the boundary caps and roof plate in the rat embryo at 13.5 days of gestation, when DRG neurons were extending their axons to the neural tube. The distributions of laminin and tenascin appeared, respectively, to be slightly and considerably different from that of neurocan.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Competition and cooperation between tenascin-R, lecticans and contactin 1 regulate neurite growth and morphology.

The extracellular matrix molecule tenascin-R (TN-R) and the proteoglycans of the lectican family show an overlapping distribution in the developing brain, have been implicated in similar cellular processes and form a complex network of interactions. Previously, we have demonstrated that TN-R induces microprocesses along neurites and enlarged growth cones of tectal cells by interacting with the cell adhesion molecule contactin 1. Here, we describe competition and cooperation between TN-R, lecticans and contactin 1, and their functional consequences for tectal cells. Aggrecan, brevican and neurocan inhibit the effects of TN-R on microprocess formation and growth cone size. This blocking effect is due to competition of lecticans with binding of TN-R to its neuronal receptor contactin 1, as shown by a sandwich-binding assay. Interaction of aggrecan with TN-R fibronectin type III domains 4-A is necessary for its inhibitory effect on both microprocess formation and TN-R binding to contactin 1. However, the chondroitin sulfate chains are not involved. Time-lapse video microscopy showed that aggrecan has no acute effect on motility and morphology of microprocesses and growth cones but induces long-term neurite retraction after pre-treatment with TN-R. In contrast to the competition described above, TN-R cooperates with brevican and neurocan to induce attachment of tectal cells and neurite outgrowth, probably by forming a bridge between the lectican substrate and contactin 1 as the neuronal receptor. Our findings suggest that a complex network of protein-protein interactions within the brain extracellular matrix, as shown here for TN-R and lecticans, is important for the fine-regulation of developmental processes such as microprocess formation along the neurite and neurite outgrowth.

Aggrecans↗
PubMed2003

Perisynaptic barrier of proteoglycans in the mature brain and spinal cord.

Cell bodies and their dendrites of motor neurons, motor-related neurons, and certain other subsets of neurons such as GABAergic interneurons in the mature brain and spinal cord possess intensely negatively charged perineuronal or perisynaptic nets of proteoglycans which are linked to the nerve cell surface glycoproteins. These perineuronal nets of proteoglycans are digested by chondroitinase ABC, hyaluronidase, or collagenase, but not by endo-alpha-N-acetylgalactosaminidase, which is reactive to the nerve cell surface glycoproteins. Aggrecan, versican, neurocan, and brevican are members of a family of chondroitin sulfate proteoglycans that bind to hyaluronan. Neurocan- or brevican-deficient mice showed a regionally heterogeneous composition of proteoglycans in perineuronal nets. Aggrecan glycoforms contribute to the molecular heterogeneity of the perineuronal nets. Proteoglycans such as phosphacan are included in matrix-associated proteoglycans. The extracellular matrix glycoprotein tenascin-R is accumulated in the perineuronal nets. The perineuronal proteoglycans are produced by associated satellite astrocytes just before weaning, while the nerve cell surface glycoproteins are produced by the associated nerve cells at earlier stages after birth. The perineuronal proteoglycans may entrap the tissue fluid and form a perineuronal gel layer which protects the synapses as a "perisynaptic barrier". Degradation of the perineuronal proteoglycans or perisynaptic barrier by treatment with chondroitinase ABC or hyaluronidase reactivates the neuronal plasticity or promotes the functional recovery of a severed nervous system. Another set of perineuronal nets occurs, which are intensely positively charged and contain guanidino compounds. It is considered that these intensely positively charged nets are intermingled with the intensely negatively charged ones of proteoglycans.

Animals↗
PubMed1994

[Expression of the extracellular matrix proteoglycan, versican, in human skin].

Extracellular matrix chondroitin/dermatan sulfate proteoglycans are present in a wide variety of tissues including cartilage, placenta, aorta, tendon, brain and skin. They possibly participate in cellular processes such as cell adhesion, migration and proliferation. Recently, we have determined the entire primary structure of the large fibroblast proteoglycan, versican, on the basis of its cDNA sequence. Versican belongs to the family of large aggregating proteoglycans. Other members of the family, which have been characterized in terms of their primary structure, are aggrecan in cartilage and neurocan isolated from brain tissues. Due to the extensive sequence similarities between these three proteoglycans in the N- and C-terminal domains and due to the high degree of carbohydrate substitution, the generation of antibodies monospecific for versican has been difficult. To avoid cross-reactivity with aggrecan and neurocan, we therefore prepared unique portions of versican in a bacterial expression system and used them to immunize rabbits (Zimmermann et al., 1994). The affinity-purified anti-fusion protein antibodies specifically reacted with intact versican from an osteosarcoma cell line. First immunohistochemical experiments on cryo-sections of human skin revealed anti-versican staining in the stratum basale of the epidermis, as well as in the papillary and reticular layers of the dermis. By indirect immunofluorescence, Northern and Western blotting we could demonstrate that both, dermal fibroblasts and keratinocytes express versican in primary cultures. A striking inverse correlation between versican expression and cell density was observed. Analogous to the in vivo situation, keratinocytes induced to terminally differentiate ceased to express versican.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗