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 (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.
Mery
L
L
Division of Infectious Diseases, Geneva University Hospital, Switzerland.
Magnino
F
F
Schmidt
K
K
Krause
K H
KH
Dufour
J F
JF
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015220:Calcium Channels / Q000737:chemistry* / Q000145:classification / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000737:chemistry* / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D050052:TRPC Cation Channels; D014018:Tissue Distribution; D020798:Two-Hybrid System Techniques
D015220:Calcium Channels; D017931:DNA Primers; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D050052:TRPC Cation Channels; C104603:TRPC3 cation channel; C489571:TRPC4 ion channel; C096351:transient receptor potential cation channel, subfamily C, member 1