title: The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide.
abstract: The calcitonin (CT)-like (CL) receptor is a CT gene-related peptide (CGRP) receptor or an adrenomedullin (AM) receptor when co-expressed with receptor-activity-modifying proteins (RAMP) 1 or 2, respectively. The CL receptor shows 57% overall sequence identity with the CT receptor, but the homology is much lower in the extreme N-terminus. An N-terminal deletion mutant of the human (h) CL receptor (Delta18-hCL) and a chimeric receptor consisting of the N-terminal amino acids of the porcine (p) CT receptor fused to the Delta18-hCL receptor (pCT-hCL) were therefore analyzed. The Delta18-hCL receptor function was abolished when co-expressed with RAMP1 or -2. The pCT-hCL receptor was a fully functional CGRP receptor when co-expressed with RAMP1, but the RAMP2-dependent AM receptor function was impaired. Limited sequence similarities in the N-terminus of the pCT and the hCL receptors rescue CGRP but not AM receptor binding and signalling.
authors.affiliation: Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstrasse 340, 8008, Zurich, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Koller
authors.forename: Walter
authors.initials: W
authors.lastname: Born
authors.forename: Kerstin
authors.initials: K
authors.lastname: Leuthäuser
authors.forename: Beat
authors.initials: B
authors.lastname: Flühmann
authors.forename: R Anne
authors.initials: RA
authors.lastname: McKinney
authors.forename: Jan A
authors.initials: JA
authors.lastname: Fischer
authors.forename: Roman
authors.initials: R
authors.lastname: Muff
mesh_terms: D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D058286:Calcitonin Receptor-Like Protein; D006224:Cricetinae; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D011485:Protein Binding; D018003:Receptors, Calcitonin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D010455:Peptides; D018003:Receptors, Calcitonin; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide