The alternatively spliced deltae13 transcript of the rabbit calcitonin receptor dimerizes with the C1a isoform and inhibits its surface expression.
Numerous alternatively spliced transcripts are generated from the gene for the G protein-coupled calcitonin receptor, and some of the splice variants show differences in receptor-mediated signaling events. This study showed that the deltae13 splice variant of the rabbit calcitonin receptor is expressed together with the more common C1a in osteoclast-like cells. Since other G protein-coupled receptors form homo- or heterodimers, we examined whether heterodimerization of the calcitonin receptor splice variants occurs and, if so, whether it affects the function of the receptor. Homodimers of both isoforms and deltae13/C1a heterodimers were detected by co-immunoprecipitation and fluorescence resonance energy transfer analysis. In contrast to the C1a isoform, the deltae13 isoform was not efficiently transported to the cell surface. When co-expressed with the C1a splice variant, the deltae13 isoform colocalized with the C1a isoform within the cell but not at the cell surface. Furthermore, the overexpression of the deltae13 variant led to a significant reduction of the C1a surface expression and consequently a reduction of the cAMP response and Erk phosphorylation after ligand stimulation. We therefore suggest that the deltae13 variant of the rabbit calcitonin receptor acts to regulate the surface expression of the C1a isoform.
Seck
Thomas
T
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510, USA. thomas_seck@hotmail.com
Baron
Roland
R
Horne
William C
WC
D017398:Alternative Splicing; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D019204:GTP-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation; D014644:Genetic Variation; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics; D011817:Rabbits; D018003:Receptors, Calcitonin / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic; D014162:Transfection
D020033:Protein Isoforms; D018003:Receptors, Calcitonin; D019204:GTP-Binding Proteins