HETEROTETRAMERIC COMPLEX-FORMATION OF INOSITOL 1,4,5-TRISPHOSPHATE RECEPTOR SUBUNITS

The inositol 1,4,5-trisphosphate receptor (IP(3)R) exists as a tetrame ric complex to form a functional inositol 1,4,5-trisphosphate-gated Ca 2+ channel. Molecular cloning studies have shown that there are at lea st three types of IP(3)R subunits, designated type 1, type 2, and type 3. The levels of expression of IP(3)R subunits in various cell lines were investigated by Western blot analysis using type-specific antibod ies against 15 C-terminal amino acids of each IP(3)R subunit. We found that all the three types of IP(3)R subunits were expressed in each ce ll line examined, but their levels of expression varied. To determine whether IP(3)Rs form heterotetramers, we employed immunoprecipitation experiments using Chinese hamster ovary cells (CHO-K1 cells), in which all three types are abundantly expressed. Each type-specific antibody immunoprecipitated not only the respective cognate type but also the other two types. This result suggests that distinct types of IP(3)R su bunits assemble to form heterotetramers in CHO-K1 cells. We also detec ted heterotetramers in rat liver, in which IP(3)R type 1 and type 2 ar e expressed abundantly. Previous studies have shown some functional di fferences among IP(3)R types, suggesting the possibility that various compositions of subunits show distinct channel properties. The diversi ty of IP(3)R channels may be further increased by the co-assembly of d ifferent IP(3)R subunits to form home- or heterotetramers.