Tyr-167/Trp-168 in Type 1/3 Inositol 1,4,5-trisphosphate Receptor Mediates Functional Coupling Between Ligand Binding and Channel Opening

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2010 Sep 4

PMID 20813840

Citations 30

Authors

Haruka Yamazaki

Jenny Chan

Mitsuhiko Ikura

Takayuki Michikawa

Katsuhiko Mikoshiba

Affiliations

Soon will be listed here.

Abstract

The N-terminal ∼220-amino acid region of the inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R)/Ca(2+) release channel has been referred to as the suppressor/coupling domain because it is required for both IP(3) binding suppression and IP(3)-induced channel gating. Measurements of IP(3)-induced Ca(2+) fluxes of mutagenized mouse type 1 IP(3)R (IP(3)R1) showed that the residues responsible for IP(3) binding suppression in this domain were not essential for channel opening. On the other hand, a single amino acid substitution of Tyr-167 to alanine completely impaired IP(3)-induced Ca(2+) release without reducing the IP(3) binding activity. The corresponding residue in type 3 IP(3)R (IP(3)R3), Trp-168, was also critical for channel opening. Limited trypsin digestion experiments showed that the trypsin sensitivities of the C-terminal gatekeeper domain differed markedly between the wild-type channel and the Tyr-167 mutant under the optimal conditions for channel opening. These results strongly suggest that the Tyr/Trp residue (Tyr-167 in IP(3)R1 and Trp-168 in IP(3)R3) is critical for the functional coupling between IP(3) binding and channel gating by maintaining the structural integrity of the C-terminal gatekeeper domain at least under activation gating.

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References

Saneyoshi T, Kume S, Amasaki Y, Mikoshiba K . The Wnt/calcium pathway activates NF-AT and promotes ventral cell fate in Xenopus embryos. Nature. 2002; 417(6886):295-9. DOI: 10.1038/417295a. View

Monkawa T, Miyawaki A, Sugiyama T, Yoneshima H, Furuichi T, Saruta T . Heterotetrameric complex formation of inositol 1,4,5-trisphosphate receptor subunits. J Biol Chem. 1995; 270(24):14700-4. DOI: 10.1074/jbc.270.24.14700. View

Matsu-Ura T, Michikawa T, Inoue T, Miyawaki A, Yoshida M, Mikoshiba K . Cytosolic inositol 1,4,5-trisphosphate dynamics during intracellular calcium oscillations in living cells. J Cell Biol. 2006; 173(5):755-65. PMC: 2063891. DOI: 10.1083/jcb.200512141. View

Boehning D, Joseph S . Direct association of ligand-binding and pore domains in homo- and heterotetrameric inositol 1,4,5-trisphosphate receptors. EMBO J. 2000; 19(20):5450-9. PMC: 313997. DOI: 10.1093/emboj/19.20.5450. View

Kaftan E, Ehrlich B, WATRAS J . Inositol 1,4,5-trisphosphate (InsP3) and calcium interact to increase the dynamic range of InsP3 receptor-dependent calcium signaling. J Gen Physiol. 1997; 110(5):529-38. PMC: 2229389. DOI: 10.1085/jgp.110.5.529. View

WATRAS J, Bezprozvanny I, Ehrlich B . Inositol 1,4,5-trisphosphate-gated channels in cerebellum: presence of multiple conductance states. J Neurosci. 1991; 11(10):3239-45. PMC: 6575433. View

Grynkiewicz G, Poenie M, Tsien R . A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985; 260(6):3440-50. View

Sugawara H, Kurosaki M, Takata M, Kurosaki T . Genetic evidence for involvement of type 1, type 2 and type 3 inositol 1,4,5-trisphosphate receptors in signal transduction through the B-cell antigen receptor. EMBO J. 1997; 16(11):3078-88. PMC: 1169926. DOI: 10.1093/emboj/16.11.3078. View

Tu H, Wang Z, Bezprozvanny I . Modulation of mammalian inositol 1,4,5-trisphosphate receptor isoforms by calcium: a role of calcium sensor region. Biophys J. 2004; 88(2):1056-69. PMC: 1305112. DOI: 10.1529/biophysj.104.049601. View

10.

Nakayama T, Hattori M, Uchida K, Nakamura T, Tateishi Y, Bannai H . The regulatory domain of the inositol 1,4,5-trisphosphate receptor is necessary to keep the channel domain closed: possible physiological significance of specific cleavage by caspase 3. Biochem J. 2003; 377(Pt 2):299-307. PMC: 1223858. DOI: 10.1042/BJ20030599. View

11.

Sienaert I, Missiaen L, De Smedt H, Parys J, Sipma H, Casteels R . Molecular and functional evidence for multiple Ca2+-binding domains in the type 1 inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1997; 272(41):25899-906. DOI: 10.1074/jbc.272.41.25899. View

12.

Finch E, Turner T, Goldin S . Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release. Science. 1991; 252(5004):443-6. DOI: 10.1126/science.2017683. View

13.

Uchida K, Miyauchi H, Furuichi T, Michikawa T, Mikoshiba K . Critical regions for activation gating of the inositol 1,4,5-trisphosphate receptor. J Biol Chem. 2003; 278(19):16551-60. DOI: 10.1074/jbc.M300646200. View

14.

Yoshikawa F, Uchiyama T, Iwasaki H, Tanaka T, Furuichi T, Mikoshiba K . High efficient expression of the functional ligand binding site of the inositol 1,4,5-triphosphate receptor in Escherichia coli. Biochem Biophys Res Commun. 1999; 257(3):792-7. DOI: 10.1006/bbrc.1999.0498. View

15.

Hisatsune C, Yasumatsu K, Takahashi-Iwanaga H, Ogawa N, Kuroda Y, Yoshida R . Abnormal taste perception in mice lacking the type 3 inositol 1,4,5-trisphosphate receptor. J Biol Chem. 2007; 282(51):37225-31. DOI: 10.1074/jbc.M705641200. View

16.

Sienaert I, De Smedt H, Parys J, Missiaen L, Vanlingen S, Sipma H . Characterization of a cytosolic and a luminal Ca2+ binding site in the type I inositol 1,4,5-trisphosphate receptor. J Biol Chem. 1996; 271(43):27005-12. DOI: 10.1074/jbc.271.43.27005. View

17.

Miyawaki A, Furuichi T, Maeda N, Mikoshiba K . Expressed cerebellar-type inositol 1,4,5-trisphosphate receptor, P400, has calcium release activity in a fibroblast L cell line. Neuron. 1990; 5(1):11-8. DOI: 10.1016/0896-6273(90)90029-f. View

18.

Colquhoun D . Binding, gating, affinity and efficacy: the interpretation of structure-activity relationships for agonists and of the effects of mutating receptors. Br J Pharmacol. 1998; 125(5):924-47. PMC: 1565672. DOI: 10.1038/sj.bjp.0702164. View

19.

Galvan D, Borrego-Diaz E, Perez P, Mignery G . Subunit oligomerization, and topology of the inositol 1,4, 5-trisphosphate receptor. J Biol Chem. 1999; 274(41):29483-92. DOI: 10.1074/jbc.274.41.29483. View

20.

Furuichi T, Kohda K, Miyawaki A, Mikoshiba K . Intracellular channels. Curr Opin Neurobiol. 1994; 4(3):294-303. DOI: 10.1016/0959-4388(94)90089-2. View