The Bell-shaped Ca2+ Dependence of the Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Is Modulated by Ca2+/Calmodulin

Missiaen, Ludwig; Parys, Jan B.; Weidema, A. Freek; Sipma, Henk; Vanlingen, Sara; Smet, Patrick De; Callewaert, Geert; Smedt, Humbert De

doi:10.1074/jbc.274.20.13748

Cited by 85 publications

(68 citation statements)

References 25 publications

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“…3A shows a dose-re- . This is in accordance with our previously obtained data in A7r5 cells (14). In contrast, the addition of MLCK peptide (1 or 10 M) had no effect on the EC 50 value for Ca 2ϩ release compared with the control condition.…”

Section: Cam-binding Peptide Derived From Mlck Decreases the Ip 3 Rsupporting

confidence: 82%

“…From the observation that the dissociation takes several minutes, it can be expected that the affinity is in the nanomolar or subnanomolar range. 3 -Previously, we have shown that adding exogenous CaM to permeabilized cells inhibited IICR (14,17). This inhibition is Ca 2ϩ -and IP 3 -dependent.…”

Section: Cam-binding Peptide Derived From Mlck Decreases the Ip 3 Rmentioning

confidence: 99%

“…2ϩ -dependent way in various cell types expressing different combinations of IP 3 R isoforms (14,16,31). In a previous study, we have shown that the Ca 2ϩ -dependent inhibition occurs through binding of CaM to the N-terminal Ca 2ϩ -independent CaM-binding site.…”

Section: Remains Unclear Exogenous Cam Inhibits Iicr In a Camentioning

confidence: 99%

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Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Kasri

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Galione

et al. 2006

Journal of Biological Chemistry

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Calmodulin (CaM) is a ubiquitous Ca2؉ sensor protein that plays an important role in regulating a large number of Ca 2؉ channels, including the inositol 1,4,5-trisphosphate receptor (IP 3 R). Despite many efforts, the exact mechanism by which CaM regulates the IP 3 R still remains elusive. Here we show, using unidirectional 45 (17). This can be explained by the large conformational change that the IP 3 R undergoes in the presence of Ca 2ϩ and which may be necessary for CaM action. This interaction may provide a tonic regulation of IP 3 R activity and can explain the low sensitivity of the IP 3 R in neuronal tissues where CaM is highly expressed. The role of the Ca 2ϩ -dependent CaM-binding site in the regulatory domain, however, still remains to be elucidated.CaM-binding sites have not merely been identified as regulatory sites but have also recently been implicated in inter-and intrasubunit interactions. For example, the CaM-binding domain of the RyR1 modulates channel activity by at least two mechanisms: 1) by direct binding of CaM and 2) by forming a bridge between two different regions on the RyR1. Peptides of the RyR1 were used to demonstrate that the CaM-binding region is indeed directly involved in intersubunit interactions between the RyR subunits (18). In the case of small conductance K ϩ channels, CaM is involved in intersubunit interactions. Functional small conductance K ϩ channels are heteromeric complexes with CaM, which is constitutively associated with the ␣-subunits in a Ca 2ϩ -independent manner (19). In this study, we investigated whether endogenously bound CaM is essential for IP 3 R functioning. To test this hypothesis, we measured IP 3 R activity in the presence of different synthetic peptides corresponding to the CaM-binding region of myosin light-chain kinase (MLCK), which has a very high affinity for CaM, and in the presence of peptides corresponding to CaM-binding sites of the IP 3 R and other

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Section: Cam-binding Peptide Derived From Mlck Decreases the Ip 3 Rsupporting

confidence: 82%

Section: Cam-binding Peptide Derived From Mlck Decreases the Ip 3 Rmentioning

confidence: 99%

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Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Kasri

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Galione

et al. 2006

Journal of Biological Chemistry

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“…CaM is a ubiquitously expressed, EF-hand containing, Ca 2þ -binding protein that serves as the Ca 2þ -sensor for many cellular events (Gnegy 1993). All IP 3 R subtypes are inhibited by Ca 2þ -CaM Michikawa et al 1999;Missiaen et al 1999;Adkins et al 2000;Missiaen et al 2000), and CaM has been shown to restore Ca 2þ inhibition to purified IP 3 R Michikawa et al 1999;Nosyreva et al 2002). Yet, it has proven difficult to relate these functional effects of CaM to either its effects on IP 3 binding or to identified CaM-binding sites within IP 3 R. CaM inhibits IP 3 binding to IP 3 R1 in a Ca 2þ -independent manner (Patel et al 1997;Cardy and Taylor 1998), through a site that probably lies within the SD (Adkins et al 2000;Sienaert et al 2002).…”

Section: Regulation Of Ip 3 Receptors By Ca 2þ and Ipmentioning

confidence: 99%

IP3 Receptors: Toward Understanding Their Activation

Taylor¹,

Tovey²

2010

Cold Spring Harbor Perspectives in Biology

250

183

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Inositol 1,4,5-trisphosphate receptors (IP 3 R) and their relatives, ryanodine receptors, are the channels that most often mediate Ca 2þ release from intracellular stores. Their regulation by Ca 2þ allows them also to propagate cytosolic Ca 2þ signals regeneratively. This brief review addresses the structural basis of IP 3 R activation by IP 3 and Ca 2þ . IP 3 initiates IP 3 R activation by promoting Ca 2þ binding to a stimulatory Ca 2þ -binding site, the identity of which is unresolved. We suggest that interactions of critical phosphate groups in IP 3 with opposite sides of the clam-like IP 3 -binding core cause it to close and propagate a conformational change toward the pore via the adjacent N-terminal suppressor domain. The pore, assembled from the last pair of transmembrane domains and the intervening pore loop from each of the four IP 3 R subunits, forms a structure in which a luminal selectivity filter and a gate at the cytosolic end of the pore control cation fluxes through the IP 3 R.

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“…CaM came to the scene as it was demonstrated to ubiquitously bind and regulate IP 3 R (29,(42)(43)(44). CaM pulldown assay was performed by incubating CaM-conjugated agarose with cell lysates of Jurkat or J.Vav1, respectively, or using plain agarose beads as a negative control.…”

Section: Vav1 Interacts With Calmodulin Via Ch Domain In a Camentioning

confidence: 99%

The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes

Zhou¹,

Yin²,

Dou

et al. 2007

Journal of Biological Chemistry

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Vav1 is a guanine nucleotide exchange factor that is expressed specifically in hematopoietic cells and plays important roles in T cell development and activation. Vav1 consists of multiple structural domains so as to facilitate both its guanine nucleotide exchange activity and scaffold function following T cell antigen receptor ( Stimulation of the T cell antigen receptor (TCR)2 initiates a cascade of signaling events that lead to T cell activation. Calcium plays a central role in this process and has been studied intensively (1-4). Engagement of TCR triggers the activation and accumulation of enzymes and adapter molecules to the proximal membrane (5, 6), such as tyrosine phosphorylation and activation of phospholipase-C␥1 (PLC-␥1), thereby increasing the production of inositol 1,4,5-trisphosphate (IP 3 ). IP 3 binds to and activates the inositol 1,4,5-trisphosphate receptor (IP 3 R), which results in Ca 2ϩ release from the endoplasmic reticulum (ER) and the subsequent calcium influx from Ca 2ϩ release-activated Ca 2ϩ channel (CRAC) (1, 7). The elevated cytoplasmic [Ca 2ϩ ] i evokes a multitude of cellular responses, such as the NFAT-mediated gene expressions and the cell proliferation (8, 9).Vav1 is expressed specifically in hematopoietic cells as a 95-kDa protein, which plays pivotal roles as a guanine exchange factor (GEF) for small GTPases as well as a scaffold protein in the activation of hematopoietic cells (10 -12). The importance of Vav1 is because of its multiple structural elements, including a calponin homology (CH) domain, an acidic motif, a Dbl homology domain, a pleckstrin homology (PH) domain, a cysteine-rich motif, and one single SH2 domain flanked by two SH3 domains responsible for signaling protein assembly (12, 13). Upon TCR engagement, Vav1 is phosphorylated on the key tyrosine residues in the acidic motif, leading to the exposure of active Dbl homology domain for GDP/GTP exchange activity (14). Studies on vav1 Ϫ/Ϫ T cells isolated from knock-out mice demonstrated that Vav1 is essential for normal T cell activation and proliferation (15)(16)(17). In addition, the vav1-null cell line, J.Vav1, derived from Jurkat cells by somatic gene targeting approach, also exhibits pleiotropic defects in TCR-mediated signaling pathways (18).T cell stimulation evokes a biphasic calcium flux as follows: calcium release from intracellular stores followed by calcium influx across the plasma membrane (7,19). IP 3 Rs dominantly control the initiation of IP 3 -induced calcium release, demonstrated by using antisense knockdown of IP 3 R to block calcium release from the ER (20). Jurkat T cells express three IP 3 R isoforms, IP 3 R-1, IP 3 R-2, and IP 3 R-3 (21), which differ significantly in their sensitivity to IP 3 (22,23). A tyrosine kinase, Fyn, was suggested to modulate IP 3 R channel activities (24,25). Interactions between IP 3 R and other proteins, such as calmodulin (CaM), were reported to control the channel opening. Although some observations viewed CaM as an inhibitory protein of IP 3 R (26 -28), more...

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The Bell-shaped Ca2+ Dependence of the Inositol 1,4,5-Trisphosphate-induced Ca2+ Release Is Modulated by Ca2+/Calmodulin

Cited by 85 publications

References 25 publications

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

Endogenously Bound Calmodulin Is Essential for the Function of the Inositol 1,4,5-Trisphosphate Receptor

IP3 Receptors: Toward Understanding Their Activation

The Calponin Homology Domain of Vav1 Associates with Calmodulin and Is Prerequisite to T Cell Antigen Receptor-induced Calcium Release in Jurkat T Lymphocytes

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