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

FEBS Letters

Krause, Karl-Heinz³  Schmidt, Karin⁴  Dufour, Jean-François⁴  Mery, Laurence¹  Magnino, Fabrice² 

[1] Division of Infectious Diseases, Geneva University Hospital, CH-1211 Geneva 14, Switzerland;University Paris V, Paris, France;Department of Geriatrics, Geneva University Hospital, CH-1211 Geneva 14, Switzerland;Department of Clinical Pharmacology, University of Bern, Murtenstrasse 35, 3010 Bern, Switzerland

关键词: Transient receptor potential protein;    Inositol 1;    4;    5-triphosphate receptor;    Alternative splicing;    Ca2+ entry;    EYFP;    enhanced yellow fluorescent protein;    G3PDH;    glyceraldehyde-3-phosphate dehydrogenase;    GST;    glutathione-S-transferase;    HEK;    human embryonic kidney;    InsP3;    inositol 1;    4;    5-triphosphate;    InsP3R;    inositol 1;    4;    5-triphosphate receptor;    IRES;    internal ribosome entry site;    PCR;    polymerase chain reaction;    RACE;    rapid amplification of cDNA ends;    SDS;    sodium dodecyl sulfate;    SOC;    store-operated channels;    Trp;    Transient receptor potential;    Trpl;    Trp-like;   

DOI  :  10.1016/S0014-5793(00)02362-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 α-hTrp4 and β-hTrp4. The shorter variant β-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 α-hTrp4, but not of β-hTrp4, associates in vitro with the C-terminal domain of the InsP₃ 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.

【 授权许可】

Unknown