Identification of Common Binding Sites for Calmodulin and Inositol 1,4,5-Trisphosphate Receptors on the Carboxyl Termini of Trp Channels

Tang, Jungen; Lin, Yong; Zhang, Zongming; Tikunova, Svetlana B.; Birnbaumer, Lutz; Zhu, Michael X.

doi:10.1074/jbc.m102316200

Cited by 287 publications

(305 citation statements)

References 56 publications

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“…The mechanism by which IP 3 R activation stimulates I cat in arterial smooth muscle cells is unclear. Studies using protein overexpression have demonstrated that a consensus sequence present on the COOH terminus of all TRPC channel isoforms recognizes an NH 2 -terminal binding domain found in all IP 3 R isoforms (46). It has been proposed that physical coupling of these two domains removes inhibitory calmodulin from the TRPC channel COOH terminus, leading to channel activation (46,55).…”

Section: Discussionmentioning

confidence: 99%

“…Studies using protein overexpression have demonstrated that a consensus sequence present on the COOH terminus of all TRPC channel isoforms recognizes an NH 2 -terminal binding domain found in all IP 3 R isoforms (46). It has been proposed that physical coupling of these two domains removes inhibitory calmodulin from the TRPC channel COOH terminus, leading to channel activation (46,55). Whether a similar coupling mechanism underlies IP 3 R regulation of I cat and TRPC3 channels in arterial smooth muscle cells remains to be determined but is one possibility.…”

Section: Discussionmentioning

confidence: 99%

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Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

Zhao

Adebiyi²,

Blaskova

et al. 2008

American Journal of Physiology-Cell Physiology

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,4,5-trisphosphate receptors (IP3Rs) regulate diverse physiological functions, including contraction and proliferation. There are three IP3R isoforms, but their functional significance in arterial smooth muscle cells is unclear. Here, we investigated relative expression and physiological functions of IP3R isoforms in cerebral artery smooth muscle cells. We show that 2-aminoethoxydiphenyl borate and xestospongin C, membrane-permeant IP3R blockers, reduced Ca 2ϩ wave activation and global intracellular Ca 2ϩ ([Ca 2ϩ ]i) elevation stimulated by UTP, a phospholipase C-coupled purinergic receptor agonist. Quantitative PCR, Western blotting, and immunofluorescence indicated that all three IP3R isoforms were expressed in acutely isolated cerebral artery smooth muscle cells, with IP3R1 being the most abundant isoform at 82% of total IP3R message. IP3R1 knockdown with short hairpin RNA (shRNA) did not alter baseline Ca 2ϩ wave frequency and global [Ca 2ϩ ]i but abolished UTP-induced Ca 2ϩ wave activation and reduced the UTP-induced global [Ca 2ϩ ]i elevation by ϳ61%. Antibodies targeting IP3R1 and IP3R1 knockdown reduced UTP-induced nonselective cation current (Icat) activation. IP3R1 knockdown also reduced UTP-induced vasoconstriction in pressurized arteries with both intact and depleted sarcoplasmic reticulum (SR) Ca 2ϩ by ϳ45%. These data indicate that IP 3R1 is the predominant IP3R isoform expressed in rat cerebral artery smooth muscle cells. IP 3R1 stimulation contributes to UTP-induced I cat activation, Ca 2ϩ wave generation, global [Ca 2ϩ ]i elevation, and vasoconstriction. In addition, IP 3R1 activation constricts cerebral arteries in the absence of SR Ca 2ϩ release by stimulating plasma membrane Icat.cerebral artery smooth muscle cells; calcium wave; short hairpin RNA INOSITOL 1,4,5-trisphosphate (IP 3 ) receptors (IP 3 Rs) are expressed in many cell types and regulate several physiological functions, including development, muscle contraction, cell proliferation, and differentiation (1,45,47,56 Rs (7,43,54). IP 3 also activates cation channels in vascular smooth muscle cells through mechanisms that do not require the stimulation of sarcoplasmic reticulum (SR) Ca 2ϩ release (27, 54). In cerebral artery smooth muscle cells, IP 3 R activation stimulates TRPC3 channels, leading to Na ϩ influx, membrane depolarization, voltage-dependent Ca 2ϩ channel activation, and vasoconstriction (54). Thus IP 3 Rs regulate ion channel activity, Ca 2ϩ signals, and physiological functions in the vasculature. However, despite the functional importance of IP 3 Rs in arterial smooth muscle cells, specific IP 3 R isoforms that are expressed in this cell type and their functional significance are poorly understood.Three IP 3 R isoforms, designated IP 3 R1, IP 3 R2, and IP 3 R3, are encoded by distinct genes (6, 37). IP 3 R isoform expression varies widely between different cell types. Cerebellar Purkinje neurons express predominantly IP 3 R1, pancreatic ␤-cells primarily express IP 3 R3, and cardiac myocytes express IP 3 R2 (14, 48...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

Zhao

Adebiyi²,

Blaskova

et al. 2008

American Journal of Physiology-Cell Physiology

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“…Moreover, CaM has been shown to modulate several channels from the TRP superfamily (Boulay 2002;Numazaki et al 2003;Phillips et al 1992;Singh et al 2002;Tang et al 2001;Trost et al 1999Trost et al , 2001Warr and Kelly 1996;Zhang et al 2001). TRPV5 and TRPV6 activity is negatively regulated by the intracellular Ca 2+ concentration and CaM could mediate the regulation of the activity of both channels.…”

Section: Calmodulinmentioning

confidence: 99%

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

Abel

Hoenderop

Bindels

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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The epithelial Ca 2+ channels TRPV5 and TRPV6 represent a new family of Ca 2+ channels that belongs to the superfamily of transient receptor potential channels. TRPV5 and TRPV6 constitute the apical Ca 2+ entry mechanism in active Ca 2+ transport in kidney and intestine. The central role of TRPV5 and TRPV6 in active Ca 2+ (re)absorption makes it a prime target for regulation to maintain Ca 2+ balance. This review covers the hormonal regulation, interaction with accessory proteins and (patho)physiological implications of these epithelial Ca 2+ channels.

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“…The channel underlying the classical TRPC3 conductance, may generate divergent types of Ca 2+ signals depending on the availability of Ca 2+ -handling partner proteins in a particular tissue. Association of various Ca 2+ transport systems and Ca 2+ binding proteins with TRPC3 has been demonstrated (Kiselyov et al 1999;Tang et al 2001;Rosker et al 2004;Treves et al 2004) and it appears reasonable to speculate that TRPC3-associated Ca 2+ transport systems function as signaling partners of TRPC3 channels. Such signaling partners are considered as determinants of signal input as well as of signal output in terms of generation and tailoring the TRPC3-mediated Ca 2+ signals.…”

Section: Introductionmentioning

confidence: 97%

“…Some reports indicate that phopholipase C-signaling and the ill-defined mechanism that communicates reductions in the endoplasmic reticulum Ca 2+ content to the plasma membrane converge at TRPC3 channels due to a physical coupling between TRPC3 channels and IP 3 or ryanodine receptors in the membrane of cellular Ca 2+ stores (Kiselyov et al 1998;Kiselyov et al 2001;Tang et al 2001;Vazquez et al 2001;Zhang et al 2001). Nonetheless, evidence has been presented demonstrating that TRPC3 is able to form phospholipase Cregulated cation channels that are gated by diacylglycerol and independently of IP 3 , indicating a prominent role for the lipid messenger (Hofmann et al 1999;Trebak et al 2003).…”

Section: Introductionmentioning

confidence: 99%

TRPC3: a versatile transducer molecule that serves integration and diversification of cellular signals

Rosker

2005

Naunyn-Schmiedeberg's Arch Pharmacol

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Transient receptor potential (TRP) proteins have been recognized as sensors for a wide variety of external and internal signals involved in maintenance of cellular homeostasis and control of physiological functions. Evidence of a striking versatility in terms of signal integration and transduction has been reported for members of the canonical (or classical) TRP subfamily (TRPCs). TRPC species are cation channel subunits and emerge as multifunctional signal transduction molecules that are able to function as components of divergent signalplexes. Results obtained in heterologous expression systems suggest TRPC3 as a paradigm of multifunctional signal transduction by a cation channel protein. TRPC3 serves cellular Ca 2+ signaling by multiple mechanisms and may control a variety of distinct physiological functions. In this review, we summarize current knowledge on the properties and possible signaling partners of TRPC3, and discuss the role of TRPC3 channel proteins in cellular signaling networks.

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Identification of Common Binding Sites for Calmodulin and Inositol 1,4,5-Trisphosphate Receptors on the Carboxyl Termini of Trp Channels

Cited by 287 publications

References 56 publications

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

TRPC3: a versatile transducer molecule that serves integration and diversification of cellular signals

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Identification of Common Binding Sites for Calmodulin and Inositol 1,4,5-Trisphosphate Receptors on the Carboxyl Termini of Trp Channels

Cited by 287 publications

References 56 publications

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca2+ signals, and vasoconstriction in cerebral arteries

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca2+ signals, and vasoconstriction in cerebral arteries

The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease

TRPC3: a versatile transducer molecule that serves integration and diversification of cellular signals

Contact Info

Product

Resources

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Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries

Type 1 inositol 1,4,5-trisphosphate receptors mediate UTP-induced cation currents, Ca²⁺ signals, and vasoconstriction in cerebral arteries