tailieunhanh - Báo cáo khoa học: Calcitonin in a protochordate, Ciona intestinalis – the prototype of the vertebrate calcitonin/calcitonin gene-related peptide superfamily

The calcitonin (CT)⁄CT gene-related peptides (CGRPs) constitute a large peptide family in vertebrates. However, no CT⁄CGRP superfamily mem-bers have so far been identified in invertebrates, and the evolutionary pro-cess leading to the diverse vertebrate CT⁄CGRP superfamily members remains unclear. | Calcitonin in a protochordate Ciona intestinalis - the prototype of the vertebrate calcitonin calcitonin gene-related peptide superfamily Toshio Sekiguchi1 Nobuo Suzuki2 Nobuyuki Fujiwara1 Masato Aoyama1 Tsuyoshi Kawada1 Kenji Sugase1 Yoshiko Murata1 Yuichi Sasayama2 Michio Ogasawara3 and Honoo Satake1 1 Suntory Institute for Bioorganic Research Osaka Japan 2 Noto Marine Laboratory Institute of Nature and EnvironmentalTechnology Kanazawa University Ishikawa Japan 3 Department of Nanobiology Graduate Schoolof Advanced Integration Science Chiba University Japan Keywords ascidian calcitonin Ciona intestinalis evolution Correspondence H. Satake Suntory Institute for Bioorganic Research Wakayamadai 1-1-1 Shimamoto-cho Mishima-gun Osaka 618-8503 Japan Fax 81 75 962 2115 Tel 81 75 962 6092 E-mail satake@ Received 19 March 2009 revised 8 June 2009 accepted 12 June 2009 doi The calcitonin CT CT gene-related peptides CGRPs constitute a large peptide family in vertebrates. However no CT CGRP superfamily members have so far been identified in invertebrates and the evolutionary process leading to the diverse vertebrate CT CGRP superfamily members remains unclear. In this study we have identified an authentic invertebrate CT Ci-CT in the ascidian Ciona intestinalis which is the phylogenetically closest invertebrate chordate to vertebrates. The amino acid sequence of Ci-CT was shown to display high similarity to those of vertebrate CTs and to share CT consensus motifs including the N-terminal circular region and C-terminal amidated proline. Furthermore the Ci-CT gene was found to be the only Ciona CT CGRP superfamily gene. Ci-CT also exhibited less potent but significant activation of the human CT receptor as compared with salmon CT. Physiological analysis revealed that Ci-CT reduced the osteoclastic activity that is specific to vertebrate CTs. CD analysis demonstrated that Ci-CT weakly forms an a-helix structure. These results provide