Type I, II and III inositol 1,4,5-trisphosphate receptor co-immunoprecipitation as evidence for the existence of heterotetrameric receptor complexes.

The recently described co-expression of type I, II and III inositol 1,4,5-trisphosphate (InsP3) receptors in the same cell type has raised the issue of whether these proteins exist as homotetramers or heterotetramers. To address this question, InsP3 receptors were immunoprecipitated with specific antibodies and then probed for co-immunoprecipitating proteins. This revealed that type I, II and III InsP3 receptors co-immunoprecipitate and thus, exist in heteromeric complexes. This situation was maintained when the relative abundance of InsP3 receptors was altered radically during cell differentiation. Thus, heterotetrameric InsP3 receptors are likely to contribute towards signaling in cells expressing more than one receptor type.