title: Early coevolution of adhesive but not antiadhesive tenascin-R ligand-receptor pairs in vertebrates: a phylogenetic study.
abstract: Axon growth inhibitory CNS matrix proteins, such as tenascin-R (TN-R), have been supposed to contribute to the poor regenerative capacity of adult mammalian CNS. With regard to TN-R function in low vertebrates capable of CNS regeneration, questions of particular interest concern the (co)evolution of ligand-receptor pairs and cellular response mechanisms associated with axon growth inhibition and oligodendrocyte differentiation. We address here these questions in a series of comparative in vivo and in vitro analyses using TN-R proteins purified from different vertebrates (from fish to human). Our studies provide strong evidence that unlike TN-R of higher vertebrates, fish TN-R proteins are not repellent for fish and less repellent for mammalian neurons and do not interfere with F3/contactin- and fibronectin-mediated mammalian cell adhesion and axon growth. However, axonal repulsion is induced in fish neurons by mammalian TN-R proteins, suggesting that the intracellular inhibitory machinery induced by TN-R-F3 interactions is already present during early vertebrate evolution. In contrast to TN-R-F3, TN-R-sulfatide interactions, mediating oligodendrocyte adhesion and differentiation, are highly conserved during vertebrate evolution. Our findings thus indicate the necessity of being cautious about extrapolations of the function of ligand-receptor pairs beyond a species border and, therefore, about the phylogenetic conservation of a molecular function at the cellular/tissue level.
authors.affiliation: Neuro- and Tumor Cell Biology Group, Department of Nuclear Medicine, University of Bonn, Sigmund Freud Str. 25, 53105 Bonn, Germany. penka.pesheva@ukb.uni-bonn.de
authors.forename: Penka
authors.initials: P
authors.lastname: Pesheva
authors.forename: Rainer
authors.initials: R
authors.lastname: Probstmeier
authors.forename: Dirk M
authors.initials: DM
authors.lastname: Lang
authors.forename: Ruth
authors.initials: R
authors.lastname: McBride
authors.forename: Nai-Jen
authors.initials: NJ
authors.lastname: Hsu
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gennarini
authors.forename: Eberhard
authors.initials: E
authors.lastname: Spiess
authors.forename: Zolo
authors.initials: Z
authors.lastname: Peshev
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000494:pharmacology; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000378:metabolism*; D058966:Contactins; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D019143:Evolution, Molecular; D005353:Fibronectins / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007211:Indoles; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013433:Sulfoglycosphingolipids / Q000494:pharmacology; D019063:Tenascin / Q000378:metabolism*; D014714:Vertebrates / Q000145:classification / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D058966:Contactins; D005353:Fibronectins; D007211:Indoles; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D013433:Sulfoglycosphingolipids; D019063:Tenascin; C074638:tenascin R; C007293:DAPI