Role for myelin-associated glycoprotein as a functional tenascin-R receptor.
The expression of the immunoglobulin superfamily member myelin-associated glycoprotein (MAG) and the extracellular matrix glycoprotein tenascin-R (TN-R) by oligodendrocytes overlaps in time and space. The two molecules can be neurite outgrowth-inhibitory or -promoting depending on the neuronal cell type and the environment in which they are presented. Here we show that the two molecules directly bind to each other in vitro and that binding sites on TN-R localize to two domains, the fibrinogen domain and the epidermal growth factor-like repeat domain with the N-terminal cysteine-rich stretch. We further show by a functional assay, namely the repulsion of MAG-transfected Chinese hamster ovary cells (CHO) cells from a TN-R substrate, that MAG is part of the signalling pathway of TN-R for cell repulsion. When coated as a uniform substrate, MAG was inhibitory for neurite outgrowth of hippocampal and cerebellar neurons in vitro, when compared to poly-L-lysine, while TN-R enhanced neurite outgrowth. When added to MAG, TN-R neutralized the neurite outgrowth-inhibitory effects of MAG, presumably by blocking the neurite outgrowth-inhibitory domain of MAG.
Yang
H
H
Department of Neurobiology, Swiss Federal Institute of Technology, Hönggerberg, Zürich.
Xiao
Z C
ZC
Becker
B
B
Hillenbrand
R
R
Rougon
G
G
Schachner
M
M
D000818:Animals; D001921:Brain / Q000502:physiology*; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D004622:Embryo, Mammalian; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008813:Mice, Inbred ICR; D018992:Myelin-Associated Glycoprotein / Q000502:physiology*; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011946:Receptors, Antigen / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019063:Tenascin / Q000502:physiology*; D014162:Transfection; D014407:Tumor Cells, Cultured
D015815:Cell Adhesion Molecules; D018992:Myelin-Associated Glycoprotein; D011946:Receptors, Antigen; D011993:Recombinant Fusion Proteins; D019063:Tenascin; C028641:Tn receptor; C074638:tenascin R