Polycystin-1 Interacts with Inositol 1,4,5-Trisphosphate Receptor to Modulate Intracellular Ca2+ Signaling with Implications for Polycystic Kidney Disease

Li, Yun; Santoso, Netty; Yu, Shengqiang; Woodward, Owen M.; Qian, Feng; Guggino, William B.

doi:10.1074/jbc.m109.068916

Cited by 53 publications

(49 citation statements)

References 60 publications

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“…22 For example, experiments in which polycystin-1 is knocked down conclude that polycystin-1 amplifies IP3-induced calcium release, 23 whereas studies using heterologous overexpression of polycystin-1 reach the opposite conclusion. 9,10 Nevertheless, most studies that have measured resting intracellular calcium, endoplasmic reticulum calcium stores, and store-operated calcium entry in primary cell cultures or microdissected samples from human and rodent polycystic tissues have found them to be reduced (Table 1). 17,[23][24][25][26][27][28][29][30][31] cholangiocytes, 37 vascular smooth muscle cells, 38 and choroid plexus.…”

Section: Disruption Of Intracellular Calcium Homeostasis and Pkdmentioning

confidence: 99%

“…[6][7][8] Polycystin-1 interacts with the inositol 1,4,5-trisphosphate receptor (IP3R). 9,10 Polycystin-2 is a transient receptor potential (TRP) channel that is mainly located in the endoplasmic reticulum, where it functions as a calcium release channel, and, possibly, located in the plasma membrane. 11,12 Polycystin-1 and fibrocystin interact with, and modulate the function of, polycystin-2.…”

Section: Disruption Of Intracellular Calcium Homeostasis and Pkdmentioning

confidence: 99%

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Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease

Torres

Harris

2014

Journal of the American Society of Nephrology

244

218

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Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide. In PKD, excessive cell proliferation and fluid secretion, pathogenic interactions of mutated epithelial cells with an abnormal extracellular matrix and alternatively activated interstitial macrophages, and the disruption of mechanisms controlling tubular diameter contribute to cyst formation. Studies with animal models suggest that several diverse pathophysiologic mechanisms, including dysregulation of intracellular calcium levels and cAMP signaling, mediate these cystogenic mechanisms. This article reviews the evidence implicating calcium and cAMP as central players in a network of signaling pathways underlying the pathogenesis of PKD and considers the therapeutic relevance of treatment strategies targeting cAMP signaling.

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Section: Disruption Of Intracellular Calcium Homeostasis and Pkdmentioning

confidence: 99%

Section: Disruption Of Intracellular Calcium Homeostasis and Pkdmentioning

confidence: 99%

Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease

Torres

Harris

2014

Journal of the American Society of Nephrology

244

218

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“…Most cases of ADPKD are caused by naturally occurring mutations in two genetically interacting loci, pkd1 (85%) and pkd2 (ϳ15%) (320). pkd1 encodes a large multispanning membrane protein [PKD1 or polycystin-1 (PC1)], while pkd2 encodes a protein [PKD2 or polycystin-2 (PC2) or TRPP2], now known to belong to the TRP superfamily of ion channels (520).…”

Section: The Inductor Of the Acrosome Reaction And Its Receptormentioning

confidence: 99%

Calcium Channels in the Development, Maturation, and Function of Spermatozoa

Darszon

Nishigaki

Beltrán

et al. 2011

Physiological Reviews

320

313

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-permeable channels and located them at distinct sites in spermatozoa so that they can help fertilize the egg. New tools to study sperm ionic currents, and image intracellular Ca 2ϩ with better spatial and temporal resolution even in swimming spermatozoa, are revealing how sperm ion channels participate in fertilization. This review critically examines the involvement of Ca 2ϩ channels in multiple signaling processes needed for spermatozoa to mature, travel towards the egg, and fertilize it. Remarkably, these tiny specialized cells can express exclusive channels like CatSper for Ca 2ϩ and SLO3 for K ϩ , which are attractive targets for contraception and for the discovery of novel signaling complexes. Learning more about fertilization is a matter of capital importance; societies face growing pressure to counteract rising male infertility rates, provide safe male gamete-based contraceptives, and preserve biodiversity through improved captive breeding and assisted conception initiatives.

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“…Polycystins are able to regulate calcium channel activity not only in the cilia, but also in other cellular compartments, including the plasma membrane and ER. Indeed, PC1 and PC2 co-assembly has been seen to generate a cation-permeable current through the plasma membrane [11] , and PC1 and PC2 are known to regulate intracellular calcium release in the ER through their interaction with the inositol 1,4,5-trisphosphate receptor (IP3R) [12][13][14] . In this context, PC2 enhances calcium release from the ER by stimulating the activity of the IP3 receptor, while PC1 inhibits this process by reducing PC2-IP3R interaction via a mechanism involving the stromal interaction molecule-1 (STIM1) and the PI3K/Akt pathway [12,15] .…”

Section: Introductionmentioning

confidence: 99%

Role of calcium in polycystic kidney disease: From signaling to pathology

Mangolini

Stephanis

Aguiari

2016

WJN

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Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 (PC1), a large multi-functional membrane receptor protein able to regulate ion channel complexes, whereas polycystin-2 (PC2), encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum (ER). In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this field could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.

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Polycystin-1 Interacts with Inositol 1,4,5-Trisphosphate Receptor to Modulate Intracellular Ca2+ Signaling with Implications for Polycystic Kidney Disease

Cited by 53 publications

References 60 publications

Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease

Strategies Targeting cAMP Signaling in the Treatment of Polycystic Kidney Disease

Calcium Channels in the Development, Maturation, and Function of Spermatozoa

Role of calcium in polycystic kidney disease: From signaling to pathology

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