title: Identification and functional characterization of mouse TPO1 as a myelin membrane protein.
abstract: TPO1 is a member of the AIGP family, a unique group of proteins that contains 11 putative transmembrane domains. Expression of the rat TPO1 gene is upregulated in cultured oligodendrocytes (OLs) during development from pro-oligodendroblasts to postmitotic OLs. However, the distribution of native TPO1 protein in cultured OLs and in the brain has not been elucidated. We investigated the distribution and cellular function of TPO1 in myelinating cells of the nervous system. In mice, TPO1 gene expression was detected in the central (CNS) and peripheral (PNS) nervous systems and was markedly upregulated at postnatal days 10-20, an early phase of myelination in the mouse brain. To investigate TPO1 localization, we generated affinity-purified antibodies to synthetic peptides derived from mouse TPO1. Immunohistochemical analysis showed that TPO1 was expressed in OLs and Schwann cells but not in neurons and astrocytes. Schwann cells from trembler mice, which lack PNS myelin, had significantly decreased TPO1 expression and an altered localization pattern, suggesting that TPO1 is a functional myelin membrane protein. In OL lineage cell cultures, TPO1 was detected in A2B5+ bipolar early progenitors, A2B5+ multipolar Pro-OLs, GalC+ immature OLs and MBP+ mature OLs. The subcellular localization of TPO1 in OL lineage cells was mapped to the GM130+ Golgi in cell bodies and Fyn+ cell processes and myelin-like sheets. Furthermore, TPO1 selectively colocalized with non-phosphorylated Fyn and promoted Fyn autophosphorylation in COS7 cells, suggesting that TPO1 may play a role in myelin formation via Fyn kinase activation in the PNS and CNS.
authors.affiliation: Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Nobuna
authors.initials: N
authors.lastname: Fukazawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Ayukawa
authors.forename: Kaori
authors.initials: K
authors.lastname: Nishikawa
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohashi
authors.forename: Nobutsune
authors.initials: N
authors.lastname: Ichihara
authors.forename: Yuki
authors.initials: Y
authors.lastname: Hikawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Abe
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kudo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyama
authors.forename: Keiji
authors.initials: K
authors.lastname: Wada
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Aoki
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001921:Brain / Q000254:growth & development / Q000378:metabolism; D019556:COS Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003432:Cross-Linking Reagents / Q000494:pharmacology; D006056:Golgi Apparatus / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants / Q000378:metabolism; D009186:Myelin Sheath / Q000502:physiology*; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D009836:Oligodendroglia / Q000378:metabolism; D010525:Peripheral Nerves / Q000254:growth & development / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D051381:Rats; D012583:Schwann Cells / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; D003432:Cross-Linking Reagents; D008565:Membrane Proteins; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D051076:Proto-Oncogene Proteins c-fyn; C510635:Serinc5 protein, mouse