How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?

Flucher, Bernhard E.; Tuluc, Petronel

doi:10.1113/jp273423

Cited by 31 publications

(62 citation statements)

References 57 publications

(90 reference statements)

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“…Changes in ion channel and pump activities are the major determinants of cell membrane electrical changes in plants (Pickard & Ding, ; Véry & Sentenac, ; Shomer et al , ; Kinraide, ; Mishra et al , ; Lim et al , ; Catterall et al , ; Flucher & Tuluc, ; Perez Garcia et al , ). Indeed, calcium channel inhibitors, such as methoxyverapamil or GdCl 3 , efficiently reduced or blocked depolarization after cell ablation, as did inhibitors of chloride and potassium channels and proton pumps (Fig A and B).…”

Section: Resultsmentioning

confidence: 99%

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

et al. 2019

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Plants are exposed to cellular damage by mechanical stresses, herbivore feeding, or invading microbes. Primary wound responses are communicated to neighboring and distal tissues by mobile signals. In leaves, crushing of large cell populations activates a long-distance signal, causing jasmonate production in distal organs. This is mediated by a cation channel-mediated depolarization wave and is associated with cytosolic Ca 2+ transient currents. Here, we report that much more restricted, single-cell wounding in roots by laser ablation elicits non-systemic, regional surface potential changes, calcium waves, and reactive oxygen species (ROS) production. Surprisingly, laser ablation does not induce a robust jasmonate response, but regionally activates ethylene production and ethylene-response markers. This ethylene activation depends on calcium channel activities distinct from those in leaves, as well as a specific set of NADPH oxidases. Intriguingly, nematode attack elicits very similar responses, including membrane depolarization and regional upregulation of ethylene markers. Moreover, ethylene signaling antagonizes nematode feeding, delaying initial syncytial-phase establishment. Regional signals caused by single-cell wounding thus appear to constitute a relevant root immune response against small invaders.

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Section: Resultsmentioning

confidence: 99%

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

et al. 2019

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“…Conversely, the earlier observation showing that mutation of the Ca V 1.1 IQ motif to alanines (IQAA) resulted in the loss of EC coupling (23) could readily be explained by its disruptive effect on the association of STAC3 with Ca V 1.1. Because in skeletal muscle L-type calcium currents are limited by several other mechanisms (24), negative feedback regulation of calcium influx by CDI may be irrelevant. Finally, interference of STAC3 with CaM function in skeletal muscle may also explain why inactivation kinetics of Ca V 1.2 are dramatically reduced when it is expressed in skeletal myotubes, which endogenously express STAC3 (25)(26)(27)(28)(29).…”

Section: Discussionmentioning

confidence: 99%

STAC Proteins Associate to the IQ Domain of CaV1.2 and Inhibit Calcium-Dependent Inactivation

Campiglio

Bagneaux

Ortner

et al. 2018

Biophysical Journal

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The adaptor proteins STAC1, STAC2, and STAC3 represent a newly identified family of regulators of voltage-gated calcium channel (Ca V ) trafficking and function. The skeletal muscle isoform STAC3 is essential for excitation-contraction coupling and its mutation causes severe muscle disease. Recently, two distinct molecular domains in STAC3 were identified, necessary for its functional interaction with Ca V 1.1: the C1 domain, which recruits STAC proteins to the calcium channel complex in skeletal muscle triads, and the SH3-1 domain, involved in excitation-contraction coupling. These interaction sites are conserved in the three STAC proteins. However, the molecular domain in Ca V 1 channels interacting with the STAC C1 domain and the possible role of this interaction in neuronal Ca V 1 channels remained unknown. Using Ca V 1.2/2.1 chimeras expressed in dysgenic (Ca V 1.1) myotubes, we identified the amino acids 1,641-1,668 in the C terminus of Ca V 1.2 as necessary for association of STAC proteins. This sequence contains the IQ domain and alanine mutagenesis revealed that the amino acids important for STAC association overlap with those making contacts with the C-lobe of calcium-calmodulin (Ca/CaM) and mediating calcium-dependent inactivation of Ca V 1.2. Indeed, patch-clamp analysis demonstrated that coexpression of either one of the three STAC proteins with Ca V 1.2 opposed calcium-dependent inactivation, although to different degrees, and that substitution of the Ca V 1.2 IQ domain with that of Ca V 2.1, which does not interact with STAC, abolished this effect. These results suggest that STAC proteins associate with the Ca V 1.2 C terminus at the IQ domain and thus inhibit calcium-dependent feedback regulation of Ca V 1.2 currents.ecently STAC3 (SH3 and cysteine-rich containing protein 3) has been identified as an essential regulator of calcium channel trafficking and function in skeletal muscle excitationcontraction (EC) coupling and a mutation in STAC3 has been linked to the severe muscle disease Native American myopathy (NAM) (1, 2). Expression of STAC3 is restricted to skeletal muscle, where STAC3 associates with the voltage-gated calcium channel Ca V 1.1 and is involved in mediating voltage-induced calcium release from the sarcoplasmic reticulum (3, 4). In nonmuscle cells, STAC3 was shown to facilitate functional membrane expression of Ca V 1.1 and alter the current properties of Ca V 1.2 (5), suggesting a role of STAC proteins as an L-type calcium channel (Ca V 1) regulator. STAC3 belongs to a family of adaptor proteins that comprises two additional isoforms, STAC1 and STAC2, which are highly expressed in the brain (1).All three STAC proteins contain one C1 domain and two SH3 protein interaction domains (6). We previously demonstrated that the stable association of STAC3 to the Ca V 1 channel complex in the triads of skeletal muscle relies on the C1 domain (7). In contrast, the NAM mutation, which impairs EC coupling and is located in the SH3-1 domain of STAC3 (2-4), did not abolish the interaction with ...

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“…The sequence of the rabbit IIS3, IIS3-S4 loop and IIS4 is indicated below to show common features. (B) Working model representing the mechanism by which alternative splicing of the exon 29 modulates the biophysical properties of Ca V 1.1 (modified from [11]). In the intermediate state, D4 forms an interaction with R1 only in Ca V 1.1e, facilitating the transition to the activated state, and therefore resulting in an improved voltage sensitivity of activation compared to that of Ca V 1.1a.…”

Section: Resultsmentioning

confidence: 99%

Role of putative voltage-sensor countercharge D4 in regulating gating properties of Ca_V1.2 and Ca_V1.3 calcium channels

et al. 2018

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Voltage-dependent calcium channels (CaV) activate over a wide range of membrane potentials, and the voltage-dependence of activation of specific channel isoforms is exquisitely tuned to their diverse functions in excitable cells. Alternative splicing further adds to the stunning diversity of gating properties. For example, developmentally regulated insertion of an alternatively spliced exon 29 in the fourth voltage-sensing domain (VSD IV) of CaV1.1 right-shifts voltage-dependence of activation by 30 mV and decreases the current amplitude several-fold. Previously we demonstrated that this regulation of gating properties depends on interactions between positive gating charges (R1, R2) and a negative countercharge (D4) in VSD IV of CaV1.1. Here we investigated whether this molecular mechanism plays a similar role in the VSD IV of CaV1.3 and in VSDs II and IV of CaV1.2 by introducing charge-neutralizing mutations (D4N or E4Q) in the corresponding positions of CaV1.3 and in two splice variants of CaV1.2. In both channels the D4N (VSD IV) mutation resulted in a ̴5 mV right-shift of the voltage-dependence of activation and in a reduction of current density to about half of that in controls. However in CaV1.2 the effects were independent of alternative splicing, indicating that the two modulatory processes operate by distinct mechanisms. Together with our previous findings these results suggest that molecular interactions engaging D4 in VSD IV contribute to voltage-sensing in all examined CaV1 channels, however its striking role in regulating the gating properties by alternative splicing appears to be a unique property of the skeletal muscle CaV1.1 channel.

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How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?

Cited by 31 publications

References 57 publications

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

STAC Proteins Associate to the IQ Domain of CaV1.2 and Inhibit Calcium-Dependent Inactivation

Role of putative voltage-sensor countercharge D4 in regulating gating properties of Ca_V1.2 and Ca_V1.3 calcium channels

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How and why are calcium currents curtailed in the skeletal muscle voltage‐gated calcium channels?

Cited by 31 publications

References 57 publications

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

Single‐cell damage elicits regional, nematode‐restricting ethylene responses in roots

STAC Proteins Associate to the IQ Domain of CaV1.2 and Inhibit Calcium-Dependent Inactivation

Role of putative voltage-sensor countercharge D4 in regulating gating properties of CaV1.2 and CaV1.3 calcium channels

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Role of putative voltage-sensor countercharge D4 in regulating gating properties of Ca_V1.2 and Ca_V1.3 calcium channels