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Receptors for calcitonin gene‐related peptide and adrenomedullin: implications for skin cell biology
Author(s) -
Fischer J. A.,
Ittner L. M.,
Born W.
Publication year - 2004
Publication title -
experimental dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.108
H-Index - 96
eISSN - 1600-0625
pISSN - 0906-6705
DOI - 10.1111/j.0906-6705.2004.0212ae.x
Subject(s) - calcitonin gene related peptide , calcitonin receptor , amylin , receptor , adrenomedullin , chemistry , calcitonin , biochemistry , microbiology and biotechnology , endocrinology , biology , neuropeptide , islet , insulin
The specificity of a G‐protein‐coupled calcitonin receptor (CTR) and a CT receptor‐like receptor (CLR) for calcitonin gene‐related peptide (CGRP), adrenomedullin (AM) and amylin is defined by the heterodimeric non‐covalent association with three receptor‐activity‐modifying proteins (RAMPs). Chemical cross‐linking of proteins at the cell surface and immunoprecipitation have identified [ 125 I]CGRP/CLR/RAMP1, [ 125 I]AM/CLR/RAMP2 and ‐3 as well as [ 125 I]CGRP/CTR/RAMP1, [ 125 I]amylin/CTR/RAMP1 and ‐RAMP3 complexes. CLR/RAMP1 defines a CGRP receptor. CLR/RAMP2 and ‐3 correspond to AM1 and AM2 receptor isotypes, respectively. The AM1 receptor cross‐reacts with CGRP at high and the AM2 receptor at low concentrations. With the N‐terminal deletion of amino acids 14–20 of the mouse, CLR‐selective inactivation of AM over CGRP receptor function was obtained. As a result, functional interaction with AM was no longer possible. Overexpression of the CLR in transgenic mice together with the endogenous RAMP2 results in thinning of the hairs during postnatal development (L. M. Ittner et al. conference poster). In conclusion, the extreme N‐terminus of the CLR and the extracellular N‐terminal domains of RAMP1 and ‐2 contain amino acid residues that provide AM‐ or CGRP‐binding selectivity of the CLR/RAMP complexes. Hair development is attenuated, resulting in the thinning of the hairs and eventually alopecia during postnatal development.