title: Cleavage and oligomerization of gliomedin, a transmembrane collagen required for node of ranvier formation.
abstract: Gliomedin, which has been implicated as a major player in genesis of the nodes of Ranvier, contains two collagenous domains and an olfactomedin-like domain and belongs to the group of type II transmembrane collagens that includes collagens XIII and XVII and ectodysplasin A. One characteristic of this protein family is that constituent proteins can exist in both transmembrane and soluble forms. Recently, gliomedin expressed at the tips of Schwann cell microvilli was found to bind axonal adhesion molecules neurofascin and NrCAM in interactions essential for Na(+)-channel clustering at the nodes of Ranvier in myelinating peripheral nerves. Interestingly, exogenously added olfactomedin domain was found to have the same effect as intact gliomedin. Here we analyze the tissue form of gliomedin and demonstrate that the molecule not only exists as full-length gliomedin but also as a soluble form shed from the cell surface in a furin-dependent manner. In addition, gliomedin can be further proteolytically processed by bone morphogenetic protein 1/Tolloid-like enzymes, resulting in release of the olfactomedin domain from the collagen domains. Interestingly, the later cleavage induces formation of higher order, insoluble molecular aggregates that may play important roles in Na(+)-channel clustering.
authors.affiliation: Center for Biochemistry, Medical Faculty, University of Cologne, D-50931 Cologne, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Maertens
authors.forename: Delana
authors.initials: D
authors.lastname: Hopkins
authors.forename: Claus-Werner
authors.initials: CW
authors.lastname: Franzke
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Keene
authors.forename: Leena
authors.initials: L
authors.lastname: Bruckner-Tuderman
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Greenspan
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000378:metabolism; D001369:Axons / Q000378:metabolism; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000378:metabolism; D002522:Chlorocebus aethiops; D024181:Collagen Type XIII / Q000378:metabolism; D053331:Ectodysplasins / Q000378:metabolism; D045683:Furin / Q000378:metabolism; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D051379:Mice; D008871:Microvilli / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism; D024041:Non-Fibrillar Collagens / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011901:Ranvier's Nodes / Q000378:metabolism*; D012583:Schwann Cells / Q000378:metabolism*; D015222:Sodium Channels / Q000378:metabolism; D055394:Tolloid-Like Metalloproteinases; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D055395:Bone Morphogenetic Protein 1; D019485:Bone Morphogenetic Proteins; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D024181:Collagen Type XIII; D053331:Ectodysplasins; D045683:Furin; D008666:Metalloendopeptidases; D045726:Metalloproteases; D009414:Nerve Growth Factors; D024041:Non-Fibrillar Collagens; D015222:Sodium Channels; D055394:Tolloid-Like Metalloproteinases; D000097805:Collagen Type XVII; C506019:Eda protein, mouse; C504593:Nfasc protein, mouse; C520020:gliomedin protein, mouse; C525705:BMP1 protein, human; C525707:Bmp1 protein, mouse