14-3-3τ Promotes Surface Expression of Cav2.2 (α1B) Ca2+ Channels

Liu, Feng; Zhou, Qin; Zhou, Jie; Sun, Hao; Wang, Yan; Zou, Xinzhuo; Feng, Lingling; Hou, Zhaoyuan; Zhou, Aiwu; Zhou, Yi; Li, Yong

doi:10.1074/jbc.m114.567800

Cited by 9 publications

(9 citation statements)

References 41 publications

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“…2a, e ). A similar ‘double’ 14-3-3 interaction region has been recently reported for Ca v 2.2 channel 29 . One of the two 14-3-3 binding sites found on Ca v 2.2 contains an ER retention signal regulated by interactions with 14-3-3 proteins which allows Ca v 2.2 to exit the ER.…”

Section: Discussionsupporting

confidence: 84%

Voltage-gated sodium channels assemble and gate as dimers

et al. 2017

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Fast opening and closing of voltage-gated sodium channels are crucial for proper propagation of the action potential through excitable tissues. Unlike potassium channels, sodium channel α-subunits are believed to form functional monomers. Yet, an increasing body of literature shows inconsistency with the traditional idea of a single α-subunit functioning as a monomer. Here we demonstrate that sodium channel α-subunits not only physically interact with each other but they actually assemble, function and gate as a dimer. We identify the region involved in the dimerization and demonstrate that 14-3-3 protein mediates the coupled gating. Importantly we show conservation of this mechanism among mammalian sodium channels. Our study not only shifts conventional paradigms in regard to sodium channel assembly, structure, and function but importantly this discovery of the mechanism involved in channel dimerization and biophysical coupling could open the door to new approaches and targets to treat and/or prevent sodium channelopathies.

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Section: Discussionsupporting

confidence: 84%

Voltage-gated sodium channels assemble and gate as dimers

et al. 2017

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“…The adaptor protein 14-3-3 interacts with TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to mask a retention signal in the C-terminus of the channels, which is important for the COPI binding (Mathie et al, 2010). In fact, 14-3-3 promotes plasma membrane expression of several ion channels, such as Cav2.2 (also known as CACNA1B) (Liu et al, 2015). The effect of KCNE4 would be the opposite; by interacting with the C-terminus of Kv1.3, the ancillary peptide would hide a di-acidic forward trafficking motif important for COPII anterograde traffic.…”

Section: Discussionmentioning

confidence: 99%

The C-terminal domain of Kv1.3 regulates functional interactions with the KCNE4 subunit

Solé

Roig

Vallejo-Gracia

et al. 2016

Journal of Cell Science

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The voltage-dependent K channel Kv1.3 (also known as KCNA3), which plays crucial roles in leukocytes, physically interacts with KCNE4. This interaction inhibits the K currents because the channel is retained within intracellular compartments. Thus, KCNE subunits are regulators of K channels in the immune system. Although the canonical interactions of KCNE subunits with Kv7 channels are under intensive investigation, the molecular determinants governing the important Kv1.3- KCNE4 association in the immune system are unknown. Our results suggest that the tertiary structure of the C-terminal domain of Kv1.3 is necessary and sufficient for such an interaction. However, this element is apparently not involved in modulating Kv1.3 gating. Furthermore, the KCNE4-dependent intracellular retention of the channel, which negatively affects the activity of Kv1.3, is mediated by two independent and additive mechanisms. First, KCNE4 masks the YMVIEE signature at the C-terminus of Kv1.3, which is crucial for the surface targeting of the channel. Second, we identify a potent endoplasmic reticulum retention motif in KCNE4 that further limits cell surface expression. Our results define specific molecular determinants that play crucial roles in the physiological function of Kv1.3 in leukocytes.

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“…Interestingly, this redundancy is also observed within the channel, with some proteins interacting with more than one subunit. For example, Ca V 2.1 splicing isoforms with a shorter C-terminus that lack interaction sites for proteins like RIM or 14-3-3, can still contribute to release [162], and it is probable that this happens due to these proteins also being able to interact directly with Ca V β [17,19,163].…”

Section: Discussionmentioning

confidence: 99%

Voltage‐gated calcium channel nanodomains: molecular composition and function

Gandini

Zamponi

2021

The FEBS Journal

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Voltage-gated calcium (Ca V) channels and their regulation by proteins at the synaptic cleft play a critical role in neurotransmission. These interactions fine-tune the synaptic response through the regulation of Ca 2+ entry into the presynaptic terminal and trigger the fusion of vesicles filled with neurotransmitters and peptides. Regulation of Ca V channel intrinsic properties and their numbers at the active zones shape the timing and strength of synapses. Here, we provide an overview of a number of proteins reported to be part of Ca V channel nanodomains at the synaptic cleft and the repercussions of these interactions for Ca V channel trafficking, tethering at the active zone, and regulation of their biophysical properties. We summarize the current state of knowledge by which Ca V channels are regulated at presynaptic sites.

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14-3-3τ Promotes Surface Expression of Cav2.2 (α1B) Ca2+ Channels

Cited by 9 publications

References 41 publications

Voltage-gated sodium channels assemble and gate as dimers

Voltage-gated sodium channels assemble and gate as dimers

The C-terminal domain of Kv1.3 regulates functional interactions with the KCNE4 subunit

Voltage‐gated calcium channel nanodomains: molecular composition and function

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