Heterotetrameric complex formation of inositol 1,4,5-trisphosphate receptor subunits

Toshiaki Monkawa, Atsushi Miyawaki, Tomoyasu Sugiyama, Hiroyuki Yoneshima, Miki Yamamoto-Hino, Teiichi Furuichi, Takao Saruta, Mamoru Hasegawa, Katsuhiko Mikoshiba

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198 Citations (Scopus)


The inositol 1,4,5-trisphosphate receptor (IP3R) exists as a tetrameric complex to form a functional inositol 1,4,5-trisphosphate-gated Ca2+ channel. Molecular cloning studies have shown that there are at least three types of IP3R subunits, designated type 1, type 2, and type 3. The levels of expression of IP3R subunits in various cell lines were investigated by Western blot analysis using type-specific antibodies against 15 C-terminal amino acids of each IP3R subunit. We found that all the three types of IP3R subunits were expressed in each cell line examined, but their levels of expression varied. To determine whether IP3Rs 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 IP3R subunits assemble to form heterotetramers in CHO-K1 cells. We also detected heterotetramers in rat liver, in which IP3R type 1 and type 2 are expressed abundantly. Previous studies have shown some functional differences among IP3R types, suggesting the possibility that various compositions of subunits show distinct channel properties. The diversity of IP3R channels may be further increased by the co-assembly of different IP3R subunits to form homo- or heterotetramers.

Original languageEnglish
Pages (from-to)14700-14704
Number of pages5
JournalJournal of Biological Chemistry
Issue number24
Publication statusPublished - 1995 Jun 16

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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