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

The molecular basis of capacitative (or store-operated) Ca2+ entry is still subject to debate, The transient receptor potential proteins have been hypothesized to be structural components of store-operated Ca2+ 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(3)R). In this study, we report the existence of two isoforms of the human Trp4 protein, referred to as alpha -hTrp4 and beta -hTrp4. The shorter variant beta -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 alpha -hTrp4, but not of beta -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(3)R and me provide evidence suggesting that the formation of hTrp4-InsP(3)R complexes may be regulated by alternative splicing. (C) 2001 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.