High impact information on CSPG2

• Avian neural crest cell migration is diversely regulated by the two major hyaluronan-binding proteoglycans PG-M/versican and aggrecan [1].
• As suggested by previous in situ hybridizations, aggrecan shows a virtually opposite distribution to PG-M/versicans being confined to the perinotochordal ECM and extending dorsolaterally in a segmentally organized manner eventually to the entire spinal cord at axial levels interspacing the ganglia [1].
• Versican V2 is a major extracellular matrix component of the mature bovine brain [2].
• Having biochemical quantities of versican V2 available will allow us to test its putative modulatory role in neuronal cell adhesion and axonal growth [2].
• Versican V2 migrates after chondroitinase ABC digestion with an apparent molecular mass of about 400 kDa, whereas it barely enters a 4-15% polyacrylamide gel without the enzyme treatment [2].

Biological context of CSPG2

• PG-M/versicans V0 and V1 are shown to be the prevalent isoforms at initial and advanced phases of NC cell movement, whereas the V2 and V3 transcripts are first detected following gangliogenesis [1].
• Finally, we demonstrate that neither NiG nor Versican V2 interact with the p75(NTR)/NgR receptor complex and provide evidence that the binding sites of NiG and Nogo-66 are physically distinct from each other on neural tissue [3].
• The partial amino acid sequence analyses of the core protein clearly indicated this molecule to be versican [4].
• Versican in the theca interna adjacent to the follicular basal lamina in preovulatory follicles was not observed post ovulation, however, the granulosa cells then showed strong cytoplasmic staining for versican [5].
• In cell proliferation assays, we observed that there was greater cellular proliferation in the presence of versican G3 for both disc cell types [6].

Anatomical context of CSPG2

• Partial amino acid sequencing of bovine GHAP showed a striking identity (up to 90%) with human GHAP and with the hyaluronate binding domain of the large human fibroblast proteoglycan, versican [7].
• A glial hyaluronate-binding protein (GHAP) was isolated from bovine spinal cord and partially characterized [7].
• Our data support the notion, that intact versican V2 prevents excessive axonal growth during late phases of development and hereby participates in the structural stabilization of the mature central nervous system [8].
• In immunohistochemical and in situ hybridization experiments we show that this tissue-specific splice variant of versican is predominantly present in myelinated fiber tracts of the brain and in the optic nerve, most likely being expressed by oligodendrocytes [8].
• We demonstrate that isolated versican V2 strongly inhibits neurite outgrowth of central and peripheral neurons in stripe-choice assays using laminin-1 as permissive substrate [8].

Associations of CSPG2 with chemical compounds

• Bovine and human GHAP were demonstrated to bind specifically to hyaluronic acid (HA) with one protein molecule binding to an average 17 disaccharide repeating units [7].
• The inhibitory character of versican V2 is maintained after removal of chondroitin sulfate and N- and O-linked oligosaccharide side chains, but it is abolished after core protein digestion with proteinase-K [8].
• The CS glycoform analysis method was then applied to cartilage extract, versican, and several dermatan sulfate preparations [9].
• Other unidentified proteinases are also involved in the degradation of versican and small leucine-rich proteoglycans [10].
• On the other hand, lead decreased the accumulation of a large CS/DSPG with a core protein of approximately 450 kDa in the cell layer and the conditioned medium; the core protein was identified as versican core by Western blot analysis [11].

Other interactions of CSPG2

• Focimatrix contains collagen type IV subunits alpha1 and alpha2 (but not alpha3-alpha6), and laminin chains alpha1, beta2 and gamma1 (but not alpha2 or beta1), and nidogen-1 and perlecan (but not versican) [12].
• This study has confirmed the presence of versican and perlecan, but not the latter as a component of follicular fluid, and identified decorin and nidogen in ovarian antral follicles [13].
• Other species that were detected were biglycan and the large proteoglycans versican (splice variants V(0) and/or V(1)) and aggrecan [10].
• This work suggests a prominent role for aggrecanase enzymes in the degradation of aggrecan and to a lesser extent versican [10].

Analytical, diagnostic and therapeutic context of CSPG2

• Initial peptide mapping indicated similarities between bovine and human GHAP [7].
• Analysis of fractions following Superose 12 gel filtration chromatography by Western blotting showed that this pool of material contained the chondroitin sulphate proteoglycans versican and type IX collagen [14].
• RT-PCR amplified versican product was also associated with pericyte cultures but was not affected by BMP-2 [15].
• Glial hyaluronate-binding protein (GHAP) and a large aggregating chondroitin sulfate proteoglycan (Ag-Pg) similar to a fibroblast proteoglycan (versican) were localized in bovine, dog and cat central nervous system (CNS) gray matter by indirect immunofluorescence [16].

References