title: L-MPZ, a novel isoform of myelin P0, is produced by stop codon readthrough.
abstract: Myelin protein zero (P0 or MPZ) is a major myelin protein (∼30 kDa) expressed in the peripheral nervous system (PNS) in terrestrial vertebrates. Several groups have detected a P0-related 36-kDa (or 35-kDa) protein that is expressed in the PNS as an antigen for the serum IgG of patients with neuropathy. The molecular structure and function of this 36-kDa protein are, however, still unknown. We hypothesized that the 36-kDa protein may be derived from P0 mRNA by stop codon readthrough. We found a highly conserved region after the regular stop codon in predicted sequences from the 3'-UTR of P0 in higher animals. MS of the 36-kDa protein revealed that both P0 peptides and peptides deduced from the P0 3'-UTR sequence were found among the tryptic fragments. In transfected cells and in an in vitro transcription/translation system, the 36-kDa molecule was also produced from the identical mRNA that produced P0. We designated this 36-kDa molecule as large myelin protein zero (L-MPZ), a novel isoform of P0 that contains an additional domain at the C terminus. In the PNS, L-MPZ was localized in compact myelin. In transfected cells, just like P0, L-MPZ was localized at cell-cell adhesion sites in the plasma membrane. These results suggest that L-MPZ produced by the stop codon readthrough mechanism is potentially involved in myelination. Since this is the first finding of stop codon readthrough in a common mammalian protein, detailed analysis of L-MPZ expression will help to understand the mechanism of stop codon readthrough in mammals.
authors.affiliation: Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan. Electronic address: yoshiy@toyaku.ac.jp.
authors.forename: Yoshihide
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Hayashi
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California at Los Angeles, Los Angeles, California 90095.
authors.forename: Celia W
authors.initials: CW
authors.lastname: Campagnoni
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kimura
authors.affiliation: Department of Neurology and Geriatrics, Graduate School of Medicine, Gifu University, Gifu 501-1194, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Inuzuka
authors.affiliation: Department of Molecular Neurobiology, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo 192-0392, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Baba
mesh_terms: D000818:Animals; D002908:Chronic Disease; D018388:Codon, Terminator / Q000235:genetics / Q000378:metabolism*; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008875:Middle Aged; D018993:Myelin P0 Protein / Q000096:biosynthesis* / Q000235:genetics; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018388:Codon, Terminator; C560547:MPZ protein, human; C560546:Mpz protein, mouse; C560548:Mpz protein, rat; D018993:Myelin P0 Protein; D020033:Protein Isoforms