Differential regulation of types-1 and -3 inositol trisphosphate receptors by cytosolic Ca2+ - PubMed (original) (raw)

Differential regulation of types-1 and -3 inositol trisphosphate receptors by cytosolic Ca2+

T J Cardy et al. Biochem J. 1997.

Abstract

Biphasic regulation of inositol trisphosphate (IP3)-stimulated Ca2+ mobilization by cytosolic Ca2+ is believed to contribute to regenerative intracellular Ca2+ signals. Since cells typically express several IP3 receptor isoforms and the effects of cytosolic Ca2+ are not mediated by a single mechanism, it is important to resolve the properties of each receptor subtype. Full-length rat types-1 and -3 IP3 receptors were expressed in insect Sf9 cells at levels 10-40-fold higher than the endogenous receptors. The expressed receptors were glycosylated and assembled into tetramers, and binding of [3H]IP3 to each subtype was regulated by cytosolic Ca2+. The effects of increased [Ca2+] on native cerebellar and type-1 receptors expressed in Sf9 cells were indistinguishable. A maximally effective increase in [Ca2+] reversibly inhibited [3H]IP3 binding by approx. 50% by decreasing the number of IP3-binding sites (Bmax) without affecting their affinity for IP3. The effects of Ca2+ on type-3 receptors were more complex: increasing [Ca2+] first stimulated [3H]IP3 binding by increasing Bmax, and then inhibited it by causing a substantial decrease in the affinity of the receptor for IP3. The different effects of Ca2+ on the receptor subtypes were not a consequence of limitations in the availability of accessory proteins or of artifactual effects of Ca2+ on membrane structure. We conclude that Ca2+ can inhibit IP3 binding to types-1 and -3 IP3 receptors although by different mechanisms, and that IP3 binding to type-3 receptors is stimulated at intermediate [Ca2+]. A consequence of these differences is that, at resting cytosolic [Ca2+], type-3 receptors are more sensitive than type-1 receptors to IP3, but the situation reverses at higher cytosolic [Ca2+]. Such differences may be important in generating the spatially and temporally complex changes in cytosolic [Ca2+] evoked by receptors linked to IP3 formation.

PubMed Disclaimer

Cited by

Functional properties of Drosophila inositol trisphosphate receptors.
Swatton JE, Morris SA, Wissing F, Taylor CW. Swatton JE, et al. Biochem J. 2001 Oct 15;359(Pt 2):435-41. doi: 10.1042/0264-6021:3590435. Biochem J. 2001. PMID: 11583592 Free PMC article.
Inositol trisphosphate receptor Ca2+ release channels.
Foskett JK, White C, Cheung KH, Mak DO. Foskett JK, et al. Physiol Rev. 2007 Apr;87(2):593-658. doi: 10.1152/physrev.00035.2006. Physiol Rev. 2007. PMID: 17429043 Free PMC article. Review.
Ca2+ and calmodulin differentially modulate myo-inositol 1,4, 5-trisphosphate (IP3)-binding to the recombinant ligand-binding domains of the various IP3 receptor isoforms.
Vanlingen S, Sipma H, De Smet P, Callewaert G, Missiaen L, De Smedt H, Parys JB. Vanlingen S, et al. Biochem J. 2000 Mar 1;346 Pt 2(Pt 2):275-80. Biochem J. 2000. PMID: 10677344 Free PMC article.
Agonist-dependent phosphorylation of the inositol 1,4,5-trisphosphate receptor: A possible mechanism for agonist-specific calcium oscillations in pancreatic acinar cells.
LeBeau AP, Yule DI, Groblewski GE, Sneyd J. LeBeau AP, et al. J Gen Physiol. 1999 Jun;113(6):851-72. doi: 10.1085/jgp.113.6.851. J Gen Physiol. 1999. PMID: 10352035 Free PMC article.
Ca2+ signals initiate at immobile IP3 receptors adjacent to ER-plasma membrane junctions.
Thillaiappan NB, Chavda AP, Tovey SC, Prole DL, Taylor CW. Thillaiappan NB, et al. Nat Commun. 2017 Nov 15;8(1):1505. doi: 10.1038/s41467-017-01644-8. Nat Commun. 2017. PMID: 29138405 Free PMC article.

References

1. J Biol Chem. 1990 Jul 25;265(21):12679-85 - PubMed
1. Nature. 1989 Nov 9;342(6246):192-5 - PubMed
1. Biochem J. 1990 Aug 15;270(1):227-32 - PubMed
1. EMBO J. 1990 Dec;9(12):3893-8 - PubMed
1. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2951-5 - PubMed

Differential regulation of types-1 and -3 inositol trisphosphate receptors by cytosolic Ca2+ - PubMed (original) (raw)