TY - JOUR
T1 - Fish calcitonin receptor has novel features
AU - Nag, Kakon
AU - Kato, Akira
AU - Sultana, Naznin
AU - Ogoshi, Maho
AU - Takei, Yoshio
AU - Hirose, Shigehisa
N1 - Funding Information:
We thank Setsuko Sato for secretarial assistance. This work was supported by Grants-in-Aid for Scientific Research (14104002, 16710145, 18059010, and 06183) from the Ministry of Education, Culture, Sport, Science and Technology of Japan (MEXT) and the 21st Century COE Program of MEXT.
PY - 2007/10/12
Y1 - 2007/10/12
N2 - 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.
AB - 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.
KW - Amylin
KW - CGRP
KW - CTR
KW - GPCR
KW - Hormone-binding domain
KW - RAMP
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U2 - 10.1016/j.ygcen.2007.06.017
DO - 10.1016/j.ygcen.2007.06.017
M3 - Article
C2 - 17673213
AN - SCOPUS:34548456508
SN - 0016-6480
VL - 154
SP - 48
EP - 58
JO - General and Comparative Endocrinology
JF - General and Comparative Endocrinology
IS - 1-3
ER -
