The extreme N-terminus of the calcitonin-like receptor contributes to the selective interaction with adrenomedullin or calcitonin gene-related peptide.
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.
Koller
Daniela
D
Research Laboratory for Calcium Metabolism, Departments of Orthopaedic Surgery and Medicine, University of Zurich, Klinik Balgrist, Forchstrasse 340, 8008, Zurich, Switzerland.
Born
Walter
W
Leuthäuser
Kerstin
K
Flühmann
Beat
B
McKinney
R Anne
RA
Fischer
Jan A
JA
Muff
Roman
R
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
C545578:CALCRL protein, human; D058286:Calcitonin Receptor-Like Protein; D010455:Peptides; D018003:Receptors, Calcitonin; D053607:Adrenomedullin; D015740:Calcitonin Gene-Related Peptide