title: A complex between contactin-1 and the protein tyrosine phosphatase PTPRZ controls the development of oligodendrocyte precursor cells.
abstract: The six members of the contactin (CNTN) family of neural cell adhesion molecules are involved in the formation and maintenance of the central nervous system (CNS) and have been linked to mental retardation and neuropsychiatric disorders such as autism. Five of the six CNTNs bind to the homologous receptor protein tyrosine phosphatases gamma (PTPRG) and zeta (PTPRZ), but the biological roles of these interactions remain unclear. We report here the cocrystal structure of the carbonic anhydrase-like domain of PTPRZ bound to tandem Ig repeats of CNTN1 and combine these structural data with binding assays to show that PTPRZ binds specifically to CNTN1 expressed at the surface of oligodendrocyte precursor cells. Furthermore, analyses of glial cell populations in wild-type and PTPRZ-deficient mice show that the binding of PTPRZ to CNTN1 expressed at the surface of oligodendrocyte precursor cells inhibits their proliferation and promotes their development into mature oligodendrocytes. Overall, these results implicate the PTPRZ/CNTN1 complex as a previously unknown modulator of oligodendrogenesis.
authors.affiliation: Départment de Neuroscience, Institut Pasteur de Paris, 75624 Paris, France.
authors.forename: Smaragda
authors.initials: S
authors.lastname: Lamprianou
authors.forename: Elli
authors.initials: E
authors.lastname: Chatzopoulou
authors.forename: Jean-Léon
authors.initials: JL
authors.lastname: Thomas
authors.forename: Samuel
authors.initials: S
authors.lastname: Bouyain
authors.forename: Sheila
authors.initials: S
authors.lastname: Harroch
mesh_terms: D000818:Animals; D001665:Binding Sites; D002454:Cell Differentiation; D049109:Cell Proliferation; D058967:Contactin 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008959:Models, Neurological; D046912:Multiprotein Complexes; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism*; D055495:Neurogenesis / Q000235:genetics / Q000502:physiology; D009836:Oligodendroglia / Q000166:cytology* / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5 / Q000737:chemistry* / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012995:Solubility
chemical_list: C548669:CNTN1 protein, human; C548670:Cntn1 protein, mouse; D058967:Contactin 1; D046912:Multiprotein Complexes; D011994:Recombinant Proteins; C516896:Ptprz1 protein, mouse; D054633:Receptor-Like Protein Tyrosine Phosphatases, Class 5