Alternative splice variants of hTrp4 differentially interact with the C-terminal portion of the inositol 1,4,5-trisphosphate receptors

Abstract

The molecular basis of capacitative (or store-operated) Ca 2+ entry is still subject to debate. The transient receptor potential proteins have been hypothesized to be structural components of store-operated Ca 2+ channels and recent evidence suggests that Trp3 and its closely related homolog Trp6 are gated by the N-terminal region of the inositol 1,4,5-triphosphate receptors (InsP 3R). In this study, we report the existence of two isoforms of the human Trp4 protein, referred to as α-hTrp4 and β-hTrp4. The shorter variant β-hTrp4 is generated through alternative splicing and lacks the C-terminal amino acids G 785–S 868. Using a yeast two-hybrid assay and glutathione- S-transferase-pulldown experiments, we found that the C-terminus of α-hTrp4, but not of β-hTrp4, associates in vitro with the C-terminal domain of the InsP 3 receptors type 1, 2 and 3. Thus, we describe a novel interaction between Trp proteins and InsP 3R and we provide evidence suggesting that the formation of hTrp4–InsP 3R complexes may be regulated by alternative splicing.