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

FEBS Lett. 2001 Jan 5;487(3):377-83. doi: 10.1016/s0014-5793(00)02362-0.


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 (InsP3R). 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 G785-S868. 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 InsP3R and we provide evidence suggesting that the formation of hTrp4-InsP3R complexes may be regulated by alternative splicing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Calcium Channels / chemistry*
  • Calcium Channels / classification
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism*
  • DNA Primers / genetics
  • Humans
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate Receptors
  • Molecular Sequence Data
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Receptors, Cytoplasmic and Nuclear / chemistry*
  • Receptors, Cytoplasmic and Nuclear / classification
  • Receptors, Cytoplasmic and Nuclear / genetics
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Sequence Homology, Amino Acid
  • TRPC Cation Channels
  • Tissue Distribution
  • Two-Hybrid System Techniques


  • Calcium Channels
  • DNA Primers
  • ITPR1 protein, human
  • Inositol 1,4,5-Trisphosphate Receptors
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • TRPC Cation Channels
  • TRPC3 cation channel
  • TRPC4 ion channel
  • transient receptor potential cation channel, subfamily C, member 1