Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3

Zoukimian, Claude; Meudal, Hervé; Waard, Stephan De; Ouares, Karima Ait; Nicolas, Sébastien; Canepari, Marco; Béroud, Rémy; Landon, C.; Waard, Michel De; Boturyn, Didier

doi:10.1016/j.bmc.2018.12.009

Cited by 9 publications

(7 citation statements)

References 36 publications

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“…Although this far supralinear Ca 2ϩ signal was smaller than the supralinear Ca 2ϩ signal colocalized with the PF-mediated signal (Fig. 11A), the kinetics were qualitatively similar to those of a "supralinear" Ca 2ϩ signal obtained by blocking A-type K ϩ channels with the toxin AmmTx3 (Ait Zoukimian et al, 2019), as shown in the example in Figure 11C.…”

Section: Origin Of the Mglur1-dependent Supralinear Ca 2؉ Signals At supporting

confidence: 64%

The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

Ouares

Canepari

2020

J. Neurosci.

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In mouse cerebellar Purkinje neurons (PNs), the climbing fiber (CF) input provides a signal to parallel fiber (PF) synapses, triggering PF synapticplasticity.ThissignalisgivenbysupralinearCa 2ϩ transients,associatedwiththeCFsynapticpotentialandcolocalizedwiththePFCa 2ϩ influx, occurring only when PF activity precedes the CF input. Here, we unravel the biophysical determinants of supralinear Ca 2ϩ signals associated with paired PF-CF synaptic activity. We used membrane potential (V m) and Ca 2ϩ imaging to investigate the local CF-associated Ca 2ϩ influx following a train of PF synaptic potentials in two cases: (1) when the dendritic V m is hyperpolarized below the resting V m , and (2) when the dendriticV m isatrest.WefoundthatsupralinearCa 2ϩ signalsaremediatedbytype-1metabotropicglutamatereceptors(mGluR1s)whentheCF input is delayed by 100-150 ms from the first PF input in both cases. When the dendrite is hyperpolarized only, however, mGluR1s boost neighboring T-type channels, providing a mechanism for local coincident detection of PF-CF activity. The resulting Ca 2ϩ elevation is locally amplified by saturation of endogenous Ca 2ϩ buffers produced by the PF-associated Ca 2ϩ influx via the mGluR1-mediated nonselective cation conductance. In contrast, when the dendritic V m is at rest, mGluR1s increase dendritic excitability by inactivating A-type K ϩ channels, but this phenomenon is not restricted to the activated PF synapses. Thus, V m is likely a crucial parameter in determining PF synaptic plasticity, and the occurrence of hyperpolarization episodes is expected to play an important role in motor learning.

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Section: Origin Of the Mglur1-dependent Supralinear Ca 2؉ Signals At supporting

confidence: 64%

The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

Ouares

Canepari

2020

J. Neurosci.

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“…The unprecedented chemical control and versatility of NCL has been used to construct large libraries (with more than 100 members) of uniquely modified nucleosomes and to elucidate the mechanisms of chromatin remodeling and multivalent PTM readout (Nguyen et al, 2014;Dann et al, 2017). While NCL has not yet been applied for MAS NMR of chromatin, it has been impactful in numerous solution and MAS NMR studies of other proteins (Kwon et al, 2015;Zoukimian et al, 2019). Bypassing the need for cysteines and synthesis, single PTMs can be introduced into proteins using unnatural amino acid (UAA) incorporation by genetic means (amber suppression) (Lang and Chin, 2014) (Figure 3C).…”

Section: Chemical Biology Tools For Mas Nmr Of Modified Chromatin Samplesmentioning

confidence: 99%

Emerging Contributions of Solid-State NMR Spectroscopy to Chromatin Structural Biology

Ackermann

Debelouchina

2021

Front. Mol. Biosci.

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The eukaryotic genome is packaged into chromatin, a polymer of DNA and histone proteins that regulates gene expression and the spatial organization of nuclear content. The repetitive character of chromatin is diversified into rich layers of complexity that encompass DNA sequence, histone variants and post-translational modifications. Subtle molecular changes in these variables can often lead to global chromatin rearrangements that dictate entire gene programs with far reaching implications for development and disease. Decades of structural biology advances have revealed the complex relationship between chromatin structure, dynamics, interactions, and gene expression. Here, we focus on the emerging contributions of magic-angle spinning solid-state nuclear magnetic resonance spectroscopy (MAS NMR), a relative newcomer on the chromatin structural biology stage. Unique among structural biology techniques, MAS NMR is ideally suited to provide atomic level information regarding both the rigid and dynamic components of this complex and heterogenous biological polymer. In this review, we highlight the advantages MAS NMR can offer to chromatin structural biologists, discuss sample preparation strategies for structural analysis, summarize recent MAS NMR studies of chromatin structure and dynamics, and close by discussing how MAS NMR can be combined with state-of-the-art chemical biology tools to reconstitute and dissect complex chromatin environments.

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“…An example of this wide supralinear Ca 2+ signal is reported in Figure 10A-B. While this far supralinear Ca 2+ signal was smaller than the supralinear Ca 2+ signal co-localised with the PF-mediated signal (Figure 10A), the kinetics was qualitatively similar to that of a "supralinear" Ca 2+ signal obtained by blocking A-type K + channels with the toxin AmmTx3 (Zoukimian et al, 2019;Ait Ouares et al, 2019), as shown in the example of Figure 10C.…”

Section: Origin Of the Mglur1-dependent Supralinear Ca 2+ Signals At mentioning

confidence: 57%

The origin of physiological local mGluR1 supralinear Ca²⁺ signals in cerebellar Purkinje neurons

Ouares

Canepari

2019

Preprint

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In Purkinje neurons, the climbing fibre (CF) input provides a signal to parallel fibre (PF) synapses triggering PF synaptic plasticity. This supralinear Ca 2+ signal, co-localised with the PF Ca 2+ influx, occurs when PF activity precedes the CF input. Using membrane potential (V m ) and Ca 2+ imaging, we identified the biophysical determinants of these supralinear Ca 2+ signals. The CF-associated Ca 2+ influx is mediated by T-type or by P/Q-type Ca 2+ channels, depending on whether the dendritic V m is hyperpolarised or depolarised. The resulting Ca 2+ elevation is locally amplified by saturation of the endogenous Ca 2+ buffer produced by the PF-associated Ca 2+ influx, in particular by the slow Ca 2+ influx mediated by type-1 metabotropic glutamate receptors (mGluR1s). When the dendrite is hyperpolarised, mGluR1s boost neighbouring T-type channels providing a mechanism for local coincident detection of PF-CF activity. In contrast, when the dendrite is depolarised, mGluR1s increase dendritic excitability by inactivating A-type K + channels, but this phenomenon is not restricted to the activated PF synapses. Thus, V m is likely a crucial parameter in determining PF synaptic plasticity and the occurrence of hyperpolarisation episodes is expected to play an important role in motor learning.

show abstract

Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3

Cited by 9 publications

References 36 publications

The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

Emerging Contributions of Solid-State NMR Spectroscopy to Chromatin Structural Biology

The origin of physiological local mGluR1 supralinear Ca²⁺ signals in cerebellar Purkinje neurons

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Synthesis by native chemical ligation and characterization of the scorpion toxin AmmTx3

Cited by 9 publications

References 36 publications

The Origin of Physiological Local mGluR1 Supralinear Ca2+Signals in Cerebellar Purkinje Neurons

The Origin of Physiological Local mGluR1 Supralinear Ca2+Signals in Cerebellar Purkinje Neurons

Emerging Contributions of Solid-State NMR Spectroscopy to Chromatin Structural Biology

The origin of physiological local mGluR1 supralinear Ca2+ signals in cerebellar Purkinje neurons

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The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

The Origin of Physiological Local mGluR1 Supralinear Ca²⁺Signals in Cerebellar Purkinje Neurons

The origin of physiological local mGluR1 supralinear Ca²⁺ signals in cerebellar Purkinje neurons