title: Nuclear export of L-periaxin, mediated by its nuclear export signal in the PDZ domain.
abstract: Myelinating Schwann cells specifically express L-periaxin (L-PRX) in the mammalian peripheral nervous system. Several loss-of-function mutations in periaxin have been described and linked to autosomal recessive Dejerine Sottas neuropathy and to demyelinating Charcot-Marie-Tooth disease. The localization of L-periaxin is developmentally regulated in the nucleus and the plasma membrane of Schwann cells. In this study, L-periaxin, which contains a PDZ domain, a nuclear localization signal (NLS) domain, a repeat domain, and an acidic domain, was localized in the cytoplasm of RSC96 cells. By contrast, a mutant L-periaxin with a deleted PDZ domain was localized mainly in the nucleus of RSC96 cells. After a nuclear cyclin A1, which is localized exclusively in the nucleus, was fused with the PDZ domain, cyclinA1was found in the cytoplasm of RSC96 cells. Treatment with leptomycin B (LMB), a specific inhibitor of nuclear export mediated by leucine-rich nuclear export signal (NES), also causes nuclear accumulation of wild-type L-periaxin. Double leucine mutation (L83, 85Q) in the putative NES in the PDZ domain prevented L-periaxin nuclear export and induced nuclear accumulation. These results suggested that the localization of L-periaxin in the cytoplasm is supported by NES in the PDZ domain.
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, Shanxi, P. R. China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, Shanxi, P. R. China; Institute of Clinical Medicine and Department of Cardiology, Renmin hospital, Hubei University of Medicine, Shiyan, Hubei, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Biotechnology, Key Laboratory of Chemical Biology and Molecular Engineering of Ministry of Education, Shanxi University, Taiyuan, Shanxi, P. R. China.
authors.forename: Ting
authors.initials: T
authors.lastname: Yang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology; D007930:Leucine; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D049790:Nuclear Export Signals / Q000187:drug effects; D054731:PDZ Domains; D051381:Rats; D017384:Sequence Deletion
chemical_list: D005231:Fatty Acids, Unsaturated; D008565:Membrane Proteins; D049790:Nuclear Export Signals; C086745:periaxin; D007930:Leucine; C038753:leptomycin B