Minimal residues in linker domain of syntaxin 1A required for binding affinity to Ca<sup>2+</sup>/calmodulin‐dependent protein kinase II

Nomura, Kazushige; Ohyama, Ayako; Komiya, Yoshiaki; Igarashi, Michihiro

doi:10.1002/jnr.10563

Cited by 14 publications

(12 citation statements)

References 19 publications

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“…CaMKII has been shown to regulate exocytosis via a specific interaction with syntaxin (43)(44)(45)(46). In addition, syntaxin is known to bind to the most proximal region of the Kv2.1 C terminus, termed C1a, during Ca 2+ -facilitated exocytosis in pancreatic and other nonneuronal cells (47)(48)(49).…”

Section: Injurious Oxidant Exposure Leads To Camkii Activation In Neumentioning

confidence: 99%

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

McCord

Aizenman

2013

Proc. Natl. Acad. Sci. U.S.A.

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A simultaneous increase in cytosolic Zn 2+ and Ca 2+ accompanies the initiation of neuronal cell death signaling cascades. However, the molecular convergence points of cellular processes activated by these cations are poorly understood. Here, we show that Ca 2+ -dependent activation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is required for a cell death-enabling process previously shown to also depend on Zn 2+ . We have reported that oxidant-induced intraneuronal Zn 2+ liberation triggers a syntaxin-dependent incorporation of Kv2.1 voltage-gated potassium channels into the plasma membrane. This channel insertion can be detected as a marked enhancement of delayed rectifier K + currents in voltage clamp measurements observed at least 3 h following a short exposure to an apoptogenic stimulus. This current increase is the process responsible for the cytoplasmic loss of K + that enables protease and nuclease activation during apoptosis. In the present study, we demonstrate that an oxidative stimulus also promotes intracellular Ca 2+ release and activation of CaMKII, which, in turn, modulates the ability of syntaxin to interact with Kv2.1. Pharmacological or molecular inhibition of CaMKII prevents the K + current enhancement observed following oxidative injury and, importantly, significantly increases neuronal viability. These findings reveal a previously unrecognized cooperative convergence of Ca 2+ -and Zn 2+ -mediated injurious signaling pathways, providing a potentially unique target for therapeutic intervention in neurodegenerative conditions associated with oxidative stress.

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Section: Injurious Oxidant Exposure Leads To Camkii Activation In Neumentioning

confidence: 99%

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

McCord

Aizenman

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Reduced syntaxin 1-␣CaM kinase II and increased syntaxin 1-Munc-18 interaction in synaptic membranes after chronic antidepressants It was recently shown that syntaxin 1 reversibly binds ␣CaM kinase II and that the affinity of this interaction is greatly increased when the kinase is phosphorylated at Thr 286 (Ohyama et al, 2002;Nomura et al, 2003). It was found that the ␣CaM kinase II-binding domain of syntaxin 1, injected into presynaptic neurons, inhibits synaptic transmission, and that syntaxin 1 binds alternatively either ␣CaM kinase II or Munc-18, a presynaptic protein that was shown to block syntaxin from interacting with other SNAREs and forming the SNARE complex (Rizo and Sudhof, 2002).…”

Section: Figure 5 Effect Of Camentioning

confidence: 99%

Chronic Antidepressants Reduce Depolarization-Evoked Glutamate Release and Protein Interactions Favoring Formation of SNARE Complex in Hippocampus

Bonanno¹,

Giambelli²,

Raiteri³

et al. 2005

J. Neurosci.

212

141

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Glutamate neurotransmission was recently implicated in the action of stress and in antidepressant mechanisms. We report that chronic (not acute) treatment with three antidepressants with different primary mechanisms (fluoxetine, reboxetine, and desipramine) markedly reduced depolarization-evoked release of glutamate, stimulated by 15 or 25 mM KCl, but not release of GABA. Endogenous glutamate and GABA release was measured in superfused synaptosomes, freshly prepared from hippocampus of drug-treated rats. Interestingly, treatment with the three drugs only barely changed the release of glutamate (and of GABA) induced by ionomycin. In synaptic membranes of chronically treated rats we found a marked reduction in the protein-protein interaction between syntaxin 1 and Thr 286-phosphorylated ␣CaM kinase II (␣-calcium/calmodulin-dependent protein kinase II) (an interaction previously proposed to promote neurotransmitter release) and a marked increase in the interaction between syntaxin 1 and Munc-18 (an interaction proposed to reduce neurotransmitter release). Furthermore, we found a selective reduction in the expression level of the three proteins forming the core SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complex. These findings suggest that antidepressants work by stabilizing glutamate neurotransmission in the hippocampus and that they may represent a useful tool for the study of relationship between functional and molecular processes in nerve terminals.

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“…Intracellular Binding of CaMKII by PPM1F-A variety of proteins has been shown to interact with CaMKII such as ␣-actinin-1 (38), syntaxin 1A (52), and the NR2A subunit of N-methyl-D-aspartate receptor (53). In particular, the catalytic subunit of protein phosphatase 2A has been found to coimmunoprecipitate with CaMKII from rat ventricular myocyte lysates (54), demonstrating a physical association of CaM kinase with one of its regulating phosphatases.…”

Section: Clone J4-3 As a Potential Cam Kinase Phosphatase-j4-3mentioning

confidence: 99%

“…In addition, several deletion mutants of PPM1F were assessed to identify the region responsible for binding. Because there are no amino acid sequences in PPM1F that match those identified in other proteins to be responsible for CaMKII binding (38,52,53), we initially utilized the mutants described earlier. Fulllength as well as mutants of Myc⅐PPM1F were transiently cotransfected with mCaMKII␣ into HEK293T, and immunoprecipitates were generated using anti-Myc antibody under stringent wash conditions.…”

Section: Clone J4-3 As a Potential Cam Kinase Phosphatase-j4-3mentioning

confidence: 99%

Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts

Harvey¹,

Banga

Ozer

2004

Journal of Biological Chemistry

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The regulation of the multifunctional calcium/calmodulin dependent protein kinase II (CaMKII) by serine/ threonine protein phosphatases has been extensively studied in neuronal cells; however, this regulation has not been investigated previously in fibroblasts. We cloned a cDNA from SV40-transformed human fibroblasts that shares 80% homology to a rat calcium/calmodulin-dependent protein kinase phosphatase that encodes a PPM1F protein. By using extracts from transfected cells, PPM1F, but not a mutant (R326A) in the conserved catalytic domain, was found to dephosphorylate in vitro a peptide corresponding to the autoinhibitory region of CaMKII. Further analyses demonstrated that PPM1F specifically dephosphorylates the phospho-Thr-286 in autophosphorylated CaMKII substrate and thus deactivates the CaMKII in vitro. Coimmunoprecipitation of CaMKII with PPM1F indicates that the two proteins can interact intracellularly. Binding of PPM1F to CaMKII involves multiple regions and is not dependent on intact phosphatase activity. Furthermore, overexpression of PPM1F in fibroblasts caused a reduction in the CaMKII-specific phosphorylation of the known substrate vimentin(Ser-82) following induction of the endogenous CaM kinase. These results identify PPM1F as a CaM kinase phosphatase within fibroblasts, although it may have additional functions intracellularly since it has been presented elsewhere as POPX2 and hFEM-2. We conclude that PPM1F, possibly together with the other previously described protein phosphatases PP1 and PP2A, can regulate the activity of CaMKII. Moreover, because PPM1F dephosphorylates the critical autophosphorylation site of CaMKII, we propose that this phosphatase plays a key role in the regulation of the kinase intracellularly.The dynamic interactions between kinases and phosphatases play a critical role in the regulation of cellular processes. Because of their extensive involvement in calcium signaling (1), the multifunctional Ca 2ϩ /calmodulin-dependent protein kinase II (CaMKII) 1 and the protein phosphatases that interact with it have been the focus of several studies. In response to Ca 2ϩ -mobilizing agents, CaMKII is autophosphorylated (at Thr-286 for CaMKII␣) generating a kinase with Ca 2ϩ -independent activity (autonomous activity); however, this activity rapidly declines on removal of the stimulus (2-4), suggesting that protein phosphatases may contribute to the regulation of CaM kinase. Dephosphorylation of Thr-286 by the serine/threonine protein phosphatases PP1 (5), PP2A (6), and PP2C (7) has been shown to occur in vitro, and the phosphatase(s) responsible for regulating the endogenous CaMKII activity have been identified in a variety of cell types (7-15).Because CaMKII comprises up to 2% of the total protein in some regions of the brain, multiple investigations into the regulation of this kinase by phosphatases have been done with tissue from the central nervous system (7-12, 15). In the rat forebrain, the predominant phosphatase varies with the distinct cellular compartment; PP2A dephosphor...

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Minimal residues in linker domain of syntaxin 1A required for binding affinity to Ca²⁺/calmodulin‐dependent protein kinase II

Cited by 14 publications

References 19 publications

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

Chronic Antidepressants Reduce Depolarization-Evoked Glutamate Release and Protein Interactions Favoring Formation of SNARE Complex in Hippocampus

Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts

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Minimal residues in linker domain of syntaxin 1A required for binding affinity to Ca2+/calmodulin‐dependent protein kinase II

Cited by 14 publications

References 19 publications

Convergent Ca 2+ and Zn 2+ signaling regulates apoptotic Kv2.1 K + currents

Convergent Ca 2+ and Zn 2+ signaling regulates apoptotic Kv2.1 K + currents

Chronic Antidepressants Reduce Depolarization-Evoked Glutamate Release and Protein Interactions Favoring Formation of SNARE Complex in Hippocampus

Regulation of the Multifunctional Ca2+/Calmodulin-dependent Protein Kinase II by the PP2C Phosphatase PPM1F in Fibroblasts

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Product

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Minimal residues in linker domain of syntaxin 1A required for binding affinity to Ca²⁺/calmodulin‐dependent protein kinase II

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents

Convergent Ca ²⁺ and Zn ²⁺ signaling regulates apoptotic Kv2.1 K ⁺ currents