Association of tenascin-R with murine brain myelin membranes: involvement of divalent cations.
In the central nervous system (CNS), tenascin-R (TN-R) is mainly expressed by oligodendrocytes and in white matter tracts. Here, we have examined the molecular association of TN-R with CNS myelin by incubation of myelin membranes (MM) purified from adult mouse brain under different ionic conditions. By Western blot analysis, the 160 kDa isoform was the main TN-R component detectable in MM as a dimer which became degraded to monomers of 160 kDa and major fragments of 125 and 80 kDa in the absence of protease inhibitors. In the presence of chelating agents, TN-R was completely extracted from MM. Calcium ions promoted the dissociation of TN-R while zinc or copper blocked it. TN-R release from MM was sensitive to heat suggesting the involvement of calcium-dependent myelin protease(s) in this process. In addition, 1,10-phenanthroline (a metalloprotease blocker) partially inhibited TN-R release in the presence of calcium ions. We conclude that divalent metal ions stabilize the association of TN-R with CNS myelin and upon damage, the protein can be released and degraded by endogenous proteases, suggesting the implication of myelin-derived TN-R in axon growth inhibition and demyelinating diseases.
Pesheva
P
P
Department of Nuclear Medicine, University of Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany. pesheva@physio.uni-bonn.de
Probstmeier
R
R
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002413:Cations, Divalent / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003300:Copper / Q000378:metabolism; D019281:Dimerization; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism; D019063:Tenascin / Q000096:biosynthesis / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D002413:Cations, Divalent; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D018992:Myelin-Associated Glycoprotein; D019063:Tenascin; C074638:tenascin R; D003300:Copper; D015032:Zinc; D002118:Calcium