title: Calcitonin-typical suppression of osteoclastic activity by amphioxus calcitonin superfamily peptides and insights into the evolutionary conservation and diversity of their structures.
abstract: Calcitonin (CT) is a hormone that decreases serum calcium level by suppressing osteoclastic activity in the vertebrate bone. In vertebrates, the structure-function relationship of CTs has been studied extensively. We recently identified three CT superfamily peptides, Bf-CTFP1 to 3, and clarified the molecular and functional characteristics of their receptor and receptor activity-modifying protein in amphioxus, Branchiostoma floridae. However, the CT activity of Bf-CTFPs has yet to be investigated. In the present study, a functional analysis of Bf-CTFPs was performed using goldfish scales having both osteoclasts and osteoblasts. All Bf-CTFPs suppressed osteoclastic activity via a goldfish CT receptor. Although the primary amino acid sequences of the Bf-CTFPs showed low sequence similarity to vertebrate CTs, Bf-CTFP1 to 3 share three amino acids, Thr25, Thr27, and Pro32-NH2, that are required for receptor binding, with salmon CT. Moreover, homology model analysis revealed that the Bf-CTFPs form alpha-helical structures. The alpha-helical position and length of Bf-CTFP1 and 2 were conserved with those of a highly potent ligand, teleost CT. Interestingly, the composition of the alpha-helix of Bf-CTFP3 differed from those of teleost CT, despite that the action of Bf-CTFP3 on goldfish scales was the same as that of Bf-CTFP1 and 2. Collectively, the present study provides new insights into the structure-function relationship of CT and its functional evolution in chordates.
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Sekiguchi
authors.affiliation: Bioorganic Research Institute, Suntory Foundation for Life Sciences, 8-1-1, Seikadai, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shiraishi
authors.affiliation: Bioorganic Research Institute, Suntory Foundation for Life Sciences, 8-1-1, Seikadai, Seika-cho, Soraku-gun, Kyoto 619-0284, Japan.
authors.forename: Honoo
authors.initials: H
authors.lastname: Satake
authors.affiliation: Frontier Science Research Center, University of Miyazaki, Miyazaki, Miyazaki 889-1692, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kuwasako
authors.affiliation: National Institute for Basic Biology, Laboratory of Morphogenesis, 38 Nishigonaka Myodaiji, Okazaki 444-8585, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Sato
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan; Institute of Noto SATOUMI Education and Studies, Noto-cho, Ishikawa 927-0553, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Urata
authors.affiliation: Department of Animal Bioscience, Faculty of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Shiga 526-0829, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Wada
authors.affiliation: Department of Marine Biosciences, Division of Marine Science, Tokyo University of Marine Science and Technology, Minato-ku, Tokyo 108-8477, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Endo
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ikari
authors.affiliation: Department of Biology, College of Liberal Arts and Sciences, Tokyo Medical and Dental University, Ichikawa, Chiba 272-0827, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Hattori
authors.affiliation: Department of Zoology, D.D.U. Gorakhpur University, Gorakhpur 273-009, India.
authors.forename: Ajai K
authors.initials: AK
authors.lastname: Srivastav
authors.affiliation: Noto Marine Laboratory, Institute of Nature and Environmental Technology, Division of Marine Environmental Studies, Kanazawa University, Housu-gun, Ishikawa 927-0553, Japan. Electronic address: nobuos@staff.kanazawa-u.ac.jp.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Suzuki
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002116:Calcitonin / Q000235:genetics*; D006054:Goldfish / Q000378:metabolism*; D010455:Peptides / Q000235:genetics*; D058261:Receptor Activity-Modifying Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D058261:Receptor Activity-Modifying Proteins; D002116:Calcitonin
keywords: Alpha-helix; Amphioxus; Calcitonin; Goldfish scales; Structure-activity relationship