Fish calcitonin receptor has novel features

Kakon Nag, Akira Kato, Naznin Sultana, Maho Ogoshi, Yoshio Takei, Shigehisa Hirose

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Calcitonin (CT), a 32-amino acid peptide, was initially isolated from fish. Fish CT has higher affinity to mammalian CT receptor (CTR), and has activity on calcium homeostasis. Therefore, fish CT has been used as a drug for the treatment of human bone diseases. However, the physiological roles of CT in fish as well as the characteristics of the fish CTR have not been clarified. Here, we cloned and characterized CTR from mefugu (Takifugu obscurus). Full-length cDNA sequencing revealed that mfCTR (mf, mefugu) consists of N-terminal four tandem putative hormone-binding domains (HBDs). Database mining showed that the multiple HBD-containing CTR is a common feature for some other fishes. Detailed pharmacological studies revealed that mfCTR generated cAMP in response to (1) fish CT, (2) calcitonin gene-related peptide (CGRP) in combinations with receptor activity-modifying proteins (mfRAMPs) 1 and 4, and (3) amylin in combinations with mfRAMPs 1-5. Unlike mammalian CTR, mfCTR showed dual affinity sites. Corresponding EC50 values of those are in close proximity of the in vivo concentration of CT in fish. Analyses of the deletion mutants of mfCTR demonstrated that only the nearmost HBD to the first transmembrane region is functional to the ligands. Although, fish CT has higher affinity to the human CTR, human CT did not bind to the mfCTR. This is the first report that demonstrates the structure and property of fish receptor for CT, CGRP, and amylin. Fish CTR is the first example that has multiple HBD-like sequences.

Original languageEnglish
Pages (from-to)48-58
Number of pages11
JournalGeneral and Comparative Endocrinology
Volume154
Issue number1-3
DOIs
Publication statusPublished - Oct 12 2007
Externally publishedYes

Keywords

  • Amylin
  • CGRP
  • CTR
  • GPCR
  • Hormone-binding domain
  • RAMP

ASJC Scopus subject areas

  • Animal Science and Zoology
  • Endocrinology

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