title: An intracellular fragment of osteoactivin formed by ectodomain shedding translocated to the nucleoplasm and bound to RNA binding proteins.
abstract: Osteoactivin is a type I transmembrane protein upregulated by unloading stresses, including denervation, prolonged bed rest, and space flight, but the regulatory mechanisms of its expression and activation under these conditions remain undefined. Here we report that osteoactivin protein exists in two forms: an intact transmembrane form and a secreted form. The secreted form, the extracellular fragment of osteoactivin, was produced by ectodomain shedding and was released into a culture medium. Amino acid sequence analysis of the carboxy-terminal fragment of osteoactivin (OA-CTF) revealed that cleavage of osteoactivin by proteases occurred both at the cell surface and within the cell membrane. Localization analysis demonstrated translocalization of OA-CTF to the nucleus and the endoplasmic reticulum. Moreover, RNA binding proteins, which regulate pre-mRNA splicing, were identified as OA-CTF binding proteins. These results suggest that OA-CTF formed by ectodomain shedding is involved in the regulation of pre-mRNA splicing.
authors.affiliation: Department of Nutritional Physiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Kenro
authors.initials: K
authors.lastname: Utsunomiya
authors.forename: Kanako
authors.initials: K
authors.lastname: Owaki
authors.forename: Yuushi
authors.initials: Y
authors.lastname: Okumura
authors.forename: Momoko
authors.initials: M
authors.lastname: Yano
authors.forename: Takahiro
authors.initials: T
authors.lastname: Oto
authors.forename: Eri
authors.initials: E
authors.lastname: Suzuki
authors.forename: Seiko
authors.initials: S
authors.lastname: Tamura
authors.forename: Tomoki
authors.initials: T
authors.lastname: Abe
authors.forename: Shohei
authors.initials: S
authors.lastname: Kohno
authors.forename: Ayako
authors.initials: A
authors.lastname: Ohno
authors.forename: Katsuya
authors.initials: K
authors.lastname: Hirasaka
authors.forename: Shigetada
authors.initials: S
authors.lastname: Teshima-Kondoh
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nikawa
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000737:chemistry* / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D059748:Proteolysis; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C503043:Gpnmb protein, rat; D008562:Membrane Glycoproteins; D010446:Peptide Fragments; D016601:RNA-Binding Proteins