Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling
- PMID: 16223735
- DOI: 10.1074/jbc.M510082200
Polycystin 2 interacts with type I inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling
Abstract
Autosomal dominant polycystic kidney disease, a common cause of renal failure, arises from mutations in either the PKD1 or the PKD2 gene. The precise function of both PKD gene products polycystins (PCs) 1 and 2 remain controversial. PC2 has been localized to numerous cellular compartments, including the endoplasmic reticulum, plasma membrane, and cilia. It is unclear what pools are the most relevant to its physiological function as a putative Ca2+ channel. We employed a Xenopus oocyte Ca2+ imaging system to directly investigate the role of PC2 in inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ signaling. Cytosolic Ca2+ signals were recorded following UV photolysis of caged IP3 in the absence of extracellular Ca2+. We demonstrated that overexpression of PC2, as well as type I IP3 receptor (IP3R), significantly prolonged the half-decay time (t1/2) of IP3-induced Ca2+ transients. However, overexpressing the disease-associated PC2 mutants, the point mutation D511V, and the C-terminally truncated mutation R742X did not alter the t1/2. In addition, we found that D511V overexpression significantly reduced the amplitude of IP3-induced Ca2+ transients. Interestingly, overexpression of the C terminus of PC2 not only significantly reduced the amplitude but also prolonged the t1/2. Co-immunoprecipitation assays indicated that PC2 physically interacts with IP3R through its C terminus. Taken together, our data suggest that PC2 and IP3R functionally interact and modulate intracellular Ca2+ signaling. Therefore, mutations in either PC1 or PC2 could result in the misregulation of intracellular Ca2+ signaling, which in turn could contribute to the pathology of autosomal dominant polycystic kidney disease.
Similar articles
-
Polycystin-1 interacts with inositol 1,4,5-trisphosphate receptor to modulate intracellular Ca2+ signaling with implications for polycystic kidney disease.J Biol Chem. 2009 Dec 25;284(52):36431-36441. doi: 10.1074/jbc.M109.068916. Epub 2009 Oct 23. J Biol Chem. 2009. PMID: 19854836 Free PMC article.
-
80K-H interacts with inositol 1,4,5-trisphosphate (IP3) receptors and regulates IP3-induced calcium release activity.J Biol Chem. 2009 Jan 2;284(1):372-380. doi: 10.1074/jbc.M805828200. Epub 2008 Nov 6. J Biol Chem. 2009. PMID: 18990696
-
Calcium signaling and polycystin-2.Biochem Biophys Res Commun. 2004 Oct 1;322(4):1364-73. doi: 10.1016/j.bbrc.2004.08.043. Biochem Biophys Res Commun. 2004. PMID: 15336985 Review.
-
Inositol 1,4,5-trisphosphate [correction of tris-phosphate] activation of inositol trisphosphate [correction of tris-phosphate] receptor Ca2+ channel by ligand tuning of Ca2+ inhibition.Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15821-5. doi: 10.1073/pnas.95.26.15821. Proc Natl Acad Sci U S A. 1998. PMID: 9861054 Free PMC article.
-
Structure and function of polycystins: insights into polycystic kidney disease.Nat Rev Nephrol. 2019 Jul;15(7):412-422. doi: 10.1038/s41581-019-0143-6. Nat Rev Nephrol. 2019. PMID: 30948841 Review.
Cited by
-
Polycystins and cellular Ca2+ signaling.Cell Mol Life Sci. 2013 Aug;70(15):2697-712. doi: 10.1007/s00018-012-1188-x. Epub 2012 Oct 18. Cell Mol Life Sci. 2013. PMID: 23076254 Free PMC article. Review.
-
Strategies targeting cAMP signaling in the treatment of polycystic kidney disease.J Am Soc Nephrol. 2014 Jan;25(1):18-32. doi: 10.1681/ASN.2013040398. Epub 2013 Dec 12. J Am Soc Nephrol. 2014. PMID: 24335972 Free PMC article. Review.
-
Polycystin 2 is increased in disease to protect against stress-induced cell death.Sci Rep. 2020 Jan 15;10(1):386. doi: 10.1038/s41598-019-57286-x. Sci Rep. 2020. PMID: 31941974 Free PMC article.
-
Polycystin-1, 2, and STIM1 interact with IP(3)R to modulate ER Ca release through the PI3K/Akt pathway.Cell Physiol Biochem. 2011;27(6):715-26. doi: 10.1159/000330080. Epub 2011 Jun 17. Cell Physiol Biochem. 2011. PMID: 21691089 Free PMC article.
-
Inositol trisphosphate receptor Ca2+ release channels in neurological diseases.Pflugers Arch. 2010 Jul;460(2):481-94. doi: 10.1007/s00424-010-0826-0. Epub 2010 Apr 10. Pflugers Arch. 2010. PMID: 20383523 Free PMC article. Review.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
Miscellaneous