Receptor activity-modifying protein-dependent impairment of calcitonin receptor splice variant Δ(1–47)hCT(a) function

摘要: Background and Purpose Alternative splicing expands proteome diversity to GPCRs. Distinct receptor variants have been identified for a secretin family GPCR, the calcitonin (CTR). The possible functional contributions of these are further altered by their potential interactions with activity-modifying proteins (RAMPs). One variant human CTR lacks first 47 residues at its N terminus [Δ(1–47)hCT(a)]. However, very little is known about pharmacology this or ability interact RAMPs form amylin receptors. Experimental Approach Δ(1–47)hCT(a) was characterized both without in Cos7 and/or HEK293S cells. expression (ELISA assays) function (cAMP pERK1/2 up six agonists two antagonists were determined. Key Results Despite lacking terminus, Δ(1–47)hCT(a) still able express cell surface, but displayed generalized reduction peptide potency. retained RAMP1 formed receptor; also appeared be case RAMP3. On other hand, interaction RAMP2 resultant reduced greater extent. Conclusions Implications Δ(1–47)hCT(a) acts as surface. It exhibits function, depending on whether it associates RAMP which interacts with. Therefore, presence tissues will potentially contribute binding signalling, distribution tissues.