Bidirectional Regulation of Dendritic Voltage-Gated Potassium Channels by the Fragile X Mental Retardation Protein

Lee, Hye Young; Ge, Woo-Ping; Huang, Wendy Yajun; Yang, He; Wang, Gordon; Rowson-Baldwin, Ashley; Smith, Stephen J. J.; Jan, Yuh Nung

doi:10.1016/j.neuron.2011.11.012

Cited by 20 publications

(41 citation statements)

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“…; Lee et al . ). K v 3.1 channels play a critical role in auditory brainstem sound localisation circuits in rodents (Brown & Kaczmarek, ).…”

Section: Diagram Illustrating the Interaction Between Fmrp And Ion Chmentioning

confidence: 97%

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Fragile X mental retardation protein controls ion channel expression and activity

Ferron

2016

The Journal of Physiology

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Fragile X-associated disorders are a family of genetic conditions resulting from the partial or complete loss of fragile X mental retardation protein (FMRP). Among these disorders is fragile X syndrome, the most common cause of inherited intellectual disability and autism. FMRP is an RNA-binding protein involved in the control of local translation, which has pleiotropic effects, in particular on synaptic function. Analysis of the brain FMRP transcriptome has revealed hundreds of potential mRNA targets encoding postsynaptic and presynaptic proteins, including a number of ion channels. FMRP has been confirmed to bind voltage-gated potassium channels (K 3.1 and K 4.2) mRNAs and regulates their expression in somatodendritic compartments of neurons. Recent studies have uncovered a number of additional roles for FMRP besides RNA regulation. FMRP was shown to directly interact with, and modulate, a number of ion channel complexes. The sodium-activated potassium (Slack) channel was the first ion channel shown to directly interact with FMRP; this interaction alters the single-channel properties of the Slack channel. FMRP was also shown to interact with the auxiliary β4 subunit of the calcium-activated potassium (BK) channel; this interaction increases calcium-dependent activation of the BK channel. More recently, FMRP was shown to directly interact with the voltage-gated calcium channel, Ca 2.2, and reduce its trafficking to the plasma membrane. Studies performed on animal models of fragile X syndrome have revealed links between modifications of ion channel activity and changes in neuronal excitability, suggesting that these modifications could contribute to the phenotypes observed in patients with fragile X-associated disorders.

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“…; Lee et al . ). K v 3.1 channels play a critical role in auditory brainstem sound localisation circuits in rodents (Brown & Kaczmarek, ).…”

Section: Diagram Illustrating the Interaction Between Fmrp And Ion Chmentioning

confidence: 97%

“…; Lee et al . ). The reason for this discrepancy has not been elucidated but the use of two different mouse strains has been suggested as a possible explanation (Brager & Johnston, ).…”

Section: Diagram Illustrating the Interaction Between Fmrp And Ion Chmentioning

confidence: 97%

Fragile X mental retardation protein controls ion channel expression and activity

Ferron

2016

The Journal of Physiology

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“…The 3′‐UTR of Kv4.2 mRNA binds the RNA binding protein fragile X mental retardation protein (FMRP) – an interaction important for FMRP suppression of Kv4.2 expression in dendrites. NMDA receptor activation causes rapid dephosphorylation of the mTOR kinase, the downstream S6 kinase and its substrate FMRP, thereby relieving FMRP suppression and causing Kv4.2 up‐regulation (Lee et al 2011). This type of synaptic regulation of local translation of Kv1.1 and Kv4.2 mRNA may allow local adjustments of dendritic excitability according to synaptic activities nearby.…”

Section: Introductionmentioning

confidence: 99%

Voltage‐gated potassium channels and the diversity of electrical signalling

Jan

2012

The Journal of Physiology

211

143

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Since Hodgkin and Huxley discovered the potassium current that underlies the falling phase of action potentials in the squid giant axon, the diversity of voltage-gated potassium (Kv) channels has been manifested in multiple ways. The large and extended potassium channel family is evolutionarily conserved molecularly and functionally. Alternative splicing and RNA editing of Kv channel genes diversify the channel property and expression level. The mix-and-match of subunits in a Kv channel that contains four similar or identical pore-forming subunits and additional auxiliary subunits further diversify Kv channels. Moreover, targeting of different Kv channels to specific subcellular compartments and local translation of Kv channel mRNA in neuronal processes diversify axonal and dendritic action potentials and influence how synaptic plasticity may be modulated. As one indication of the evolutionary conservation of Kv1 channel functions, mutations of the Shaker potassium channel gene in Drosophila and the KCNA1 gene for its mammalian orthologue, Kv1.1, cause hyperexcitability near axon branch points and nerve terminals, thereby leading to uncontrolled movements and recapitulating the episodic ataxia-1 (EA1) symptoms in human patients.

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“…In contrast to alterations of global excitability, which may occur independently of synapses, localized modulations of dendritic excitability have never been observed in the absence of synaptic plasticity [6]–[9]. Kv4.2 channels play crucial role in controlling neuronal excitability by mediating transient A-type potassium currents [10], [11], have been directly associated with spatial memory in rats [12] and are implicated in a number of hyperexcitability and neurodegenerative diseases such as epilepsy [11], [13]–[15], ischemia [16], [17] and Fragile X mental retardation [18], [19]. Up to date dendritic patch clamp recordings were used to study localized changes of dendritic excitability.…”

Section: Introductionmentioning

confidence: 99%

Local Plasticity of Dendritic Excitability Can Be Autonomous of Synaptic Plasticity and Regulated by Activity-Based Phosphorylation of Kv4.2

Labno

Warrier²,

Wang³

et al. 2014

PLoS ONE

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While plasticity is typically associated with persistent modifications of synaptic strengths, recent studies indicated that modulations of dendritic excitability may form the other part of the engram and dynamically affect computational processing and output of neuronal circuits. However it remains unknown whether modulation of dendritic excitability is controlled by synaptic changes or whether it can be distinct from them. Here we report the first observation of the induction of a persistent plastic decrease in dendritic excitability decoupled from synaptic stimulation, which is localized and purely activity-based. In rats this local plasticity decrease is conferred by CamKII mediated phosphorylation of A-type potassium channels upon interaction of a back propagating action potential (bAP) with dendritic depolarization.

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Bidirectional Regulation of Dendritic Voltage-Gated Potassium Channels by the Fragile X Mental Retardation Protein

Abstract: The original publication misspelled the name of Duda Kvitsiani in the author list, which has been corrected here and in the article online.

Cited by 20 publications

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Fragile X mental retardation protein controls ion channel expression and activity

Fragile X mental retardation protein controls ion channel expression and activity

Voltage‐gated potassium channels and the diversity of electrical signalling

Local Plasticity of Dendritic Excitability Can Be Autonomous of Synaptic Plasticity and Regulated by Activity-Based Phosphorylation of Kv4.2

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