Research Topics
Genomes and Genes | Trevor J ShuttleworthSummaryAffiliation: University of Rochester Country: USA Publications
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Publications
STIM and Orai proteins and the non-capacitative ARC channelsTrevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Front Biosci 17:847-60. 2012..There is increasing evidence that the activity of these channels plays a critical role in a variety of different cellular activities...- The molecular architecture of the arachidonate-regulated Ca2+-selective ARC channel is a pentameric assembly of Orai1 and Orai3 subunitsOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
J Physiol 587:4181-97. 2009.... - Orai3--the 'exceptional' Orai?Trevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Physiol 590:241-57. 2012.... - STIM1 and the noncapacitative ARC channelsTrevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Cell Calcium 42:183-91. 2007..Precisely how this same protein can act in such separate and specific ways on these different pathways of agonist-activated Ca(2+)entry remains an intriguing, yet currently unresolved, question... 
Calcium entry and the control of calcium oscillationsT J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Biochem Soc Trans 31:916-9. 2003..At the same time the ARC channels are turned off, resulting in what we have described as a reciprocal regulation of these two distinct Ca(2+) entry pathways...- Receptor-activated calcium entry channels--who does what, and when?Trevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, 601 Elmwood Avenue, Box 711, Rochester, NY 14642, USA
Sci STKE 2004:pe40. 2004..These different channels are activated in distinct ways and operate under different conditions of stimulation... - Arachidonic acid, ARC channels, and Orai proteinsTrevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
Cell Calcium 45:602-10. 2009.... - ARC channels: a novel pathway for receptor-activated calcium entryTrevor J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
Physiology (Bethesda) 19:355-61. 2004..These signals activate calcineurin, which in turn inhibits the ARC channels, resulting in a "reciprocal regulation" of these two distinct Ca2+-entry pathways that may have important functional implications for the cell... - Agonist activation of arachidonate-regulated Ca2+-selective (ARC) channels in murine parotid and pancreatic acinar cellsOlivier Mignen
Department of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Physiol 564:791-801. 2005..This is consistent with previous reports indicating that carbachol-induced [Ca(2+)](i) signals in these cells are much more dependent on Ca(2+) entry than are the cholecystokinin-induced responses... - STIM1 regulates Ca2+ entry via arachidonate-regulated Ca2+-selective (ARC) channels without store depletion or translocation to the plasma membraneOlivier Mignen
Department of Pharmacology and Physiology, Box 711, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Physiol 579:703-15. 2007..These data demonstrate that STIM1 is a more universal regulator of Ca2+ entry pathways than previously thought, and appears to have multiple modes of action... - Both Orai1 and Orai3 are essential components of the arachidonate-regulated Ca2+-selective (ARC) channelsOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
J Physiol 586:185-95. 2008.... - Modulation of [Ca2+]i signaling dynamics and metabolism by perinuclear mitochondria in mouse parotid acinar cellsJason I E Bruce
Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Biol Chem 279:12909-17. 2004..These effects may profoundly affect a variety of nuclear processes in parotid acinar cells while facilitating efficient fluid secretion... - Arachidonate-regulated Ca2+-selective (ARC) channel activity is modulated by phosphorylation and involves an A-kinase anchoring proteinOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
J Physiol 567:787-98. 2005.... - Orai1 subunit stoichiometry of the mammalian CRAC channel poreOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
J Physiol 586:419-25. 2008..In this way we were able to demonstrate, for the first time, that the functional CRAC channel pore is formed by a tetrameric assembly of Orai1 subunits... - Ca2+-dependent protein kinase--a modulation of the plasma membrane Ca2+-ATPase in parotid acinar cellsJason I E Bruce
Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, New York 14642, USA
J Biol Chem 277:48172-81. 2002..Tight regulation of both Ca(2+) release and Ca(2+) efflux may represent a general feature of the mechanism whereby cAMP improves the fidelity and specificity of Ca(2+) signaling... - Cytosolic Ca(2+) and Ca(2+)-activated Cl(-) current dynamics: insights from two functionally distinct mouse exocrine cellsDavid R Giovannucci
Department of Pharmacology and Physiology, University of Rochester, School of Medicine and Dentistry, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Physiol 540:469-84. 2002..These data reveal specializations of common modules of Ca(2+)-release machinery and subsequent effector activation that are specifically suited to the distinct functional roles of these two related cell types... - Orai channel-dependent activation of phospholipase C-δ: a novel mechanism for the effects of calcium entry on calcium oscillationsJill L Thompson
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, NY 14642, USA
J Physiol 589:5057-69. 2011.... - Carboxyamidotriazole-induced inhibition of mitochondrial calcium import blocks capacitative calcium entry and cell proliferation in HEK-293 cellsOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA
J Cell Sci 118:5615-23. 2005.... - Ca2+ selectivity and fatty acid specificity of the noncapacitative, arachidonate-regulated Ca2+ (ARC) channelsOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, New York 14642, USA
J Biol Chem 278:10174-81. 2003..Whether this involves a direct action of arachidonic acid on the channel protein itself or an action on some intermediary molecule is, at present, unclear... - The Orai1 severe combined immune deficiency mutation and calcium release-activated Ca2+ channel function in the heterozygous conditionJill L Thompson
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 284:6620-6. 2009.... - Calcineurin directs the reciprocal regulation of calcium entry pathways in nonexcitable cellsOlivier Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 278:40088-96. 2003..Thus, calcineurin is the key mediator of the reciprocal regulation of these co-existing channels, allowing each to play a unique and non-overlapping role in Ca2+ signaling... - The N-terminal domain of Orai3 determines selectivity for activation of the store-independent ARC channel by arachidonic acidJill Thompson
Department of Pharmacology and Physiology, University of Rochester Medical Center, NY, USA
Channels (Austin) 4:398-410. 2010.... - Discriminating between capacitative and arachidonate-activated Ca(2+) entry pathways in HEK293 cellsT J Shuttleworth
Department of Pharmacology, University of Rochester School of Medicine, Rochester, New York 14642, USA
J Biol Chem 274:31174-8. 1999..These data demonstrate that the arachidonate-activated entry of Ca(2+) occurs via an entirely distinct influx pathway... - Intracellular Ca2+ signalling in secretory cellsT J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, NY 14642, USA
J Exp Biol 200:303-14. 1997..In this way, the two components responsible for the elevation of [Ca2+]i are intimately related and their dual effects closely coordinated, resulting in the finely tuned control of agonist-induced changes in [Ca2+]i... - Permeation of monovalent cations through the non-capacitative arachidonate-regulated Ca2+ channels in HEK293 cells. Comparison with endogenous store-operated channelsO Mignen
Department of Pharmacology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 276:21365-74. 2001..However, the clear differences between the properties of these currents through ARC and SOC channels in the same cell confirm that these represent distinct conductances... - Muscarinic receptor activation of arachidonate-mediated Ca2+ entry in HEK293 cells is independent of phospholipase CT J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA
J Biol Chem 273:32636-43. 1998.... - What drives calcium entry during [Ca2+]i oscillations?--challenging the capacitative modelT J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York, USA
Cell Calcium 25:237-46. 1999.... - Vertebrate salt glands: short- and long-term regulation of functionT J Shuttleworth
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, New York 14642, USA
J Exp Zool 283:689-701. 1999..This tuning of the signal involves often rather subtle changes in the overall signaling pathway that are part of the adaptive differentiation process... - Phosphorylation of inositol 1,4,5-trisphosphate receptors in parotid acinar cells. A mechanism for the synergistic effects of cAMP on Ca2+ signalingJason I E Bruce
Department of Pharmacology and Physiology, School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 277:1340-8. 2002..In addition, this report supports the emerging consensus that phosphorylation at the level of the Ca(2+) release machinery is a broadly important mechanism by which cells can regulate Ca(2+)-mediated processes... - Reciprocal regulation of capacitative and arachidonate-regulated noncapacitative Ca2+ entry pathwaysO Mignen
Department of Pharmacology and Physiology, University of Rochester Medical Center, Rochester, New York 14642, USA
J Biol Chem 276:35676-83. 2001..Importantly, these data show that at physiologically relevant levels of stimulation, it is the noncapacitative ARC channels that provide the predominant route for the agonist-activated entry of Ca(2+)... - A plasma membrane-targeted cytosolic domain of STIM1 selectively activates ARC channels, an arachidonate-regulated store-independent Orai channelJill L Thompson
Department of Pharmacology, University of Rochester Medical Center, Rochester, NY, USA
Channels (Austin) 6:370-8. 2012.... - A mathematical model of fluid secretion from a parotid acinar cellElan Gin
Department of Mathematics, The University of Auckland, Private Bag 92019, Auckland, New Zealand
J Theor Biol 248:64-80. 2007..We find that [Ca(2+)] oscillations lead to oscillations in fluid flow, and that the rate of fluid flow is regulated by the average calcium concentration and not the frequency of the oscillations...
Research Grants
- RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor Shuttleworth; Fiscal Year: 2004....
- RECEPTOR-REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor Shuttleworth; Fiscal Year: 2007....
- Signaling Pathways in Salivary Gland Fluid SecretionTrevor Shuttleworth; Fiscal Year: 2009..abstract_text> ..
- RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor Shuttleworth; Fiscal Year: 1990....
- RECEPTOR-REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor Shuttleworth; Fiscal Year: 1993..Our aim is to reproduce this expression system in culture, thereby providing a unique system for studying the specific nature of the receptor-activated Ca2+ entry mechanism, its expression and control...
- RECEPTOR REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor Shuttleworth; Fiscal Year: 2000..It may also permit the development of pharmacological agents that can be used to manipulate or modify this funddamental and widely distributed process in clinically relevant ways. ..
- RECEPTOR-REGULATED CALCIUM ENTRY IN EXOCRINE SECRETIONTrevor J Shuttleworth; Fiscal Year: 2010..Defining the molecular bases of the relevant entry pathways and their regulation, will undoubtedly help elucidate the critical mechanisms involved in their activity, and identify potential targets for their clinical manipulation. ..