title: A novel membrane-associated glycovariant of BEHAB/brevican is up-regulated during rat brain development and in a rat model of invasive glioma.
abstract: BEHAB (brain-enriched hyaluronan-binding protein)/brevican is the most abundant chondroitin sulfate proteoglycan in the extracellular matrix of the adult rat brain. BEHAB/brevican expression is up-regulated coincident with glial cell proliferation and/or motility, including during early central nervous system development and in invasive glioma. An understanding of the molecular interactions that mediate BEHAB/brevican function is still in its infancy because of the existence of several BEHAB/brevican isoforms, each of which may mediate different functions. Here, we describe a novel BEHAB/brevican isoform, B/b130, and demonstrate that it is neither the glycosylphosphatidylinositol-linked splice variant of BEHAB/brevican nor a cleavage product of the full-length protein (B/b150). B/b130 is an underglycosylated isoform of BEHAB/brevican, lacking glycosaminoglycan chains as well as most of the sugars that invest B/b150. B/b130 localizes exclusively to the particulate fraction of rat brain and associates with the cell membrane by a previously undescribed calcium-independent mechanism. In addition, B/b130 is the major isoform of BEHAB/brevican that is up-regulated in a rat model of invasive glioma and may therefore contribute to the invasive ability of glioma cells. Further understanding of BEHAB/brevican isoforms will advance our knowledge of the function of this ECM component and may help identify new potential therapeutic targets for primary brain tumors.
authors.affiliation: Department of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
authors.forename: Mariano S
authors.initials: MS
authors.lastname: Viapiano
authors.forename: Russell T
authors.initials: RT
authors.lastname: Matthews
authors.forename: Susan
authors.initials: S
authors.lastname: Hockfield
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology / Q000378:metabolism*; D058581:Brevican; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000096:biosynthesis* / Q000737:chemistry*; D018076:DNA, Complementary / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005910:Glioma / Q000378:metabolism*; D006026:Glycoside Hydrolases / Q000378:metabolism; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D007120:Immunochemistry; D007150:Immunohistochemistry; D037181:Lectins, C-Type; D051379:Mice; D008856:Microscopy, Fluorescence; D009361:Neoplasm Invasiveness; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000737:chemistry*; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: C553057:Bcan protein, mouse; C546939:Bcan protein, rat; D058581:Brevican; D002352:Carrier Proteins; D011508:Chondroitin Sulfate Proteoglycans; D018076:DNA, Complementary; D017261:Glycosylphosphatidylinositols; D037181:Lectins, C-Type; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D006026:Glycoside Hydrolases