Function and regulation of TRPP2 at the plasma membrane

Tsiokas, Leonidas

doi:10.1152/ajprenal.90277.2008

Cited by 69 publications

(66 citation statements)

References 98 publications

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“…Recently, a contribution from the TRPV4 calcium channel was confirmed which appears to function in conjuction with the TRPC1 channel (1101,1192). Polycystin-2 (PKD2 gene), a calcium channel which acts in cilia together with the mechanosensory protein polycystin-1 (PKD1 gene), also contributes significantly to these inward calcium currents (5,1287,1814). While most arterial endothelial cells are not ciliated, cilia are found frequently in atherosclerosis-prone areas, and their formation may be induced by disturbed flow (1847).…”

Section: Calcium Signaling Ion Channels and Weibel-palade Body Exocmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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At least 468 individual genes have been manipulated by molecular methods to study their effects on the initiation, promotion, and progression of atherosclerosis. Most clinicians and many investigators, even in related disciplines, find many of these genes and the related pathways entirely foreign. Medical schools generally do not attempt to incorporate the relevant molecular biology into their curriculum. A number of key signaling pathways are highly relevant to atherogenesis and are presented to provide a context for the gene manipulations summarized herein. The pathways include the following: the insulin receptor (and other receptor tyrosine kinases); Ras and MAPK activation; TNF-␣ and related family members leading to activation of NF-B; effects of reactive oxygen species (ROS) on signaling; endothelial adaptations to flow including G protein-coupled receptor (GPCR) and integrin-related signaling; activation of endothelial and other cells by modified lipoproteins; purinergic signaling; control of leukocyte adhesion to endothelium, migration, and further activation; foam cell formation; and macrophage and vascular smooth muscle cell signaling related to proliferation, efferocytosis, and apoptosis. This review is intended primarily as an introduction to these key signaling pathways. They have become the focus of modern atherosclerosis research and will undoubtedly provide a rich resource for future innovation toward intervention and prevention of the number one cause of death in the modern world.

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Section: Calcium Signaling Ion Channels and Weibel-palade Body Exocmentioning

confidence: 99%

Molecular Biology of Atherosclerosis

Hopkins

2013

Physiological Reviews

382

344

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“…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). The products of the pkd genes play key roles in renal and vascular mechanosensory transduction, in primary cilia of renal, nodal, and endothelial cells (reviewed in Ref.…”

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

314

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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“…PKD1 is a large receptor-like integral membrane protein with an extracellular Nterminus that contains motifs for cell-cell and cell-matrix interactions (Torres et al, 2007). PKD2 is a member of the TRP superfamily of nonselective Ca 2+ -permeable ion channels (Clapham, 2003) found in the plasma membrane, the endoplasmic reticulum and in the primary cilium (Cai et al, 1999;Tsiokas, 2009). Both PKD1 and PKD2 contain coiled-coil domains in their intracellular C-terminus that enables the formation of a receptorchannel complex (Casuscelli et al, 2009;Giamarchi et al, 2010;Qian et al, 1997;Tsiokas et al, 1997).…”

Section: Although Roles For Camentioning

confidence: 99%

CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia

Rothschild¹,

Francescatto²,

Drummond

et al. 2011

Development

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SUMMARY Intracellular Ca2+ signals influence gastrulation, neurogenesis and organogenesis through pathways that are still being defined. One potential Ca 2+ mediator of many of these morphogenic processes is CaMK-II, a conserved calmodulin-dependent protein kinase. Prolonged Ca 2+ stimulation converts CaMK-II into an activated state that, in the zebrafish, is detected in the forebrain, ear and kidney. Autosomal dominant polycystic kidney disease has been linked to mutations in the Ca 2+ -conducting TRP family member PKD2, the suppression of which in vertebrate model organisms results in kidney cysts. Both PKD2-deficient and CaMK-IIdeficient zebrafish embryos fail to form pronephric ducts properly, and exhibit anterior cysts and destabilized cloacal cilia. PKD2 suppression inactivates CaMK-II in pronephric cells and cilia, whereas constitutively active CaMK-II restores pronephric duct formation in pkd2 morphants. PKD2 and CaMK-II deficiencies are synergistic, supporting their existence in the same genetic pathway. We conclude that CaMK-II is a crucial effector of PKD2 Ca 2+ that both promotes morphogenesis of the pronephric kidney and stabilizes primary cloacal cilia. KEY WORDS: CaMK-II, PKD2, Cilia, Kidney, ADPKD, ZebrafishCaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia MATERIALS AND METHODS Zebrafish strains and careWild-type (AB and WIK), Tg(1 subunit Na + /K + -ATPase-GFP) and Tg(-actin:CAAX-GFP) zebrafish (Danio rerio) embryos were obtained through natural matings and raised at 28.5°C as previously described (Kimmel et al., 1995). In situ hybridizationDigoxigenin-labeled antisense riboprobes (0.5-1.5 kb) were synthesized using T3 or T7 RNA polymerase from cloned cDNAs and then hybridized with fixed embryos as previously described (Rothschild et al., 2007). For whole-mount in situ hybridization, embryos were developed using alkaline phosphatase-conjugated anti-digoxigenin. gata3, cdh17, wt1a, pax2a and ret1 probes were prepared as previously described (Wingert and Davidson, 2008;Wingert et al., 2007). A 1c antisense probe was generated from 48 hours postfertilization (hpf) kidney cDNA, TOPO cloned, linearized with NotI and transcribed using the T3 RNA polymerase. Fluorescent in situ hybridization was conducted as previously described (Rothschild et al., 2007) using fluorescent anti-digoxigenin antibodies and images were acquired using a Nikon C1 laser scanning confocal microscope. CaMK-II antibodiesImmunolocalization using anti-phosphorylated CaMK-II (anti-P-CaMK-II; phosphorylated at Thr 287 ), CaMK-II and total CaMK-II antibodies has previously been described by this laboratory (Easley et al., 2006;Francescatto et al., 2010). The anti-phospho-Thr 287 (anti-P-T 287) antibody detects CaMK-II proteins across species and the total CaMK-II antibody reacts with the C-terminal region of all CaMK-II proteins. Pronephric dissection and flow sortingNa + /K + -ATPase-GFP transgenic embryos at 24, 48 and 72 hpf were anesthetized and the pronephros dissected as previously de...

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Function and regulation of TRPP2 at the plasma membrane

Cited by 69 publications

References 98 publications

Molecular Biology of Atherosclerosis

Molecular Biology of Atherosclerosis

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

CaMK-II is a PKD2 target that promotes pronephric kidney development and stabilizes cilia

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