Heterooligomer of type 1 and type 2 inositol 1, 4, 5-trisphosphate receptor expressed in rat liver membrane fraction exists as tetrameric complex

Functional IP₃-sensitive intracellular Ca²⁺ release channel is considered to be a tetramer of IP₃R. Heterooligomeric complexes composed of distinct types of IP₃R have been reported, however, crucial evidences for them being tetramer have not appeared. Here we report that the heterooligomer composed of IP₃R1 and IP₃R2 also exists as tetramer. Cross-linked heterooligomer was immunoprecipitated with IP₃RI-specific antibody and detected by agarose-PAGE/Western blot analysis with IP₃R2-specific antibody. Tetramer, trimer, dimer, and possibly monomer were detected. The trimer, dimer, and monomer were likely to be originated from the tetramer, since: (1) the immunoprecipitating antibody (IP₃R1-specific) does not recognize IP₃R2, therefore IP₃R2 monomer itself could not have been immunoprecipitated; and (2) tetramer was the major native product of IP₃R complex containing type 2 isoform in liver membrane fraction. Thus we conclude tetramer is the native form of heterooligomer composed of IP₃R1 and IP₃R2. (C) 2000 Academic Press.