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 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 alpha-helix structure. These results provide evidence that the CT/CGRP superfamily is essentially conserved in ascidians as well as in vertebrates, and indicate that Ci-CT is a prototype of vertebrate CT/CGRP superfamily members. Moreover, expression analysis demonstrated that Ci-CT is expressed in more organs than vertebrate CTs in the cognate organs, suggesting that an original CT/CGRP superfamily member gene was also expressed in multiple organs, and each CT/CGRP superfamily member acquired its current specific tissue distribution and physiological role concomitantly with diversification of the CT/CGRP superfamily during the evolution of chordates. This is the first report on a CT/CGRP superfamily member in invertebrates.
Sekiguchi
Toshio
T
Suntory Institute for Bioorganic Research, Osaka, Japan.
Suzuki
Nobuo
N
Fujiwara
Nobuyuki
N
Aoyama
Masato
M
Kawada
Tsuyoshi
T
Sugase
Kenji
K
Murata
Yoshiko
Y
Sasayama
Yuichi
Y
Ogasawara
Michio
M
Satake
Honoo
H
D000595:Amino Acid Sequence; D000818:Animals; D002116:Calcitonin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide; D043344:Chordata; D002938:Ciona intestinalis / Q000737:chemistry*; D006801:Humans; D009928:Organ Specificity; D017433:Protein Structure, Secondary; D018003:Receptors, Calcitonin / Q000378:metabolism; D012474:Salmon; D013045:Species Specificity; D014714:Vertebrates
D018003:Receptors, Calcitonin; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide