title: Nuclear export signal-interacting protein forms complexes with lamin A/C-Nups to mediate the CRM1-independent nuclear export of large hepatitis delta antigen.
abstract: Nuclear export is an important process that not only regulates the functions of cellular factors but also facilitates the assembly of viral nucleoprotein complexes. Chromosome region maintenance 1 (CRM1) that mediates the transport of proteins bearing the classical leucine-rich nuclear export signal (NES) is the best-characterized nuclear export receptor. Recently, several CRM1-independent nuclear export pathways were also identified. The nuclear export of the large form of hepatitis delta antigen (HDAg-L), a nucleocapsid protein of hepatitis delta virus (HDV), which contains a CRM1-independent proline-rich NES, is mediated by the host NES-interacting protein (NESI). The mechanism of the NESI protein in mediating nuclear export is still unknown. In this study, NESI was characterized as a highly glycosylated membrane protein. It interacted and colocalized well in the nuclear envelope with lamin A/C and nucleoporins. Importantly, HDAg-L could be coimmunoprecipitated with lamin A/C and nucleoporins. In addition, binding of the cargo HDAg-L to the C terminus of NESI was detected for the wild-type protein but not for the nuclear export-defective HDAg-L carrying a P205A mutation [HDAg-L(P205A)]. Knockdown of lamin A/C effectively reduced the nuclear export of HDAg-L and the assembly of HDV. These data indicate that by forming complexes with lamin A/C and nucleoporins, NESI facilitates the CRM1-independent nuclear export of HDAg-L.
authors.affiliation: Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Jia-Yin
authors.initials: JY
authors.lastname: Jiang
authors.forename: Shin C
authors.initials: SC
authors.lastname: Chang
authors.forename: Yeou-Guang
authors.initials: YG
authors.lastname: Tsay
authors.forename: Mei-Ru
authors.initials: MR
authors.lastname: Chen
authors.forename: Ming-Fu
authors.initials: MF
authors.lastname: Chang
mesh_terms: D021581:Active Transport, Cell Nucleus; D003698:Hepatitis Delta Virus / Q000502:physiology*; D035923:Hepatitis delta Antigens / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D047468:Immunoprecipitation; D028884:Karyopherins / Q000378:metabolism*; D034904:Lamin Type A / Q000378:metabolism*; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism*; D029543:Nucleocytoplasmic Transport Proteins / Q000378:metabolism*; D055503:Protein Multimerization; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D019065:Virus Assembly; D000097606:Exportin 1 Protein
chemical_list: D035923:Hepatitis delta Antigens; D028884:Karyopherins; D034904:Lamin Type A; D028861:Nuclear Pore Complex Proteins; D029543:Nucleocytoplasmic Transport Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D000097606:Exportin 1 Protein; C502888:LMBRD1 protein, human; C442244:hepatitis delta virus large antigen