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Fragile X mental retardation protein controls ion channel expression and activity

Ferron, L; (2016) Fragile X mental retardation protein controls ion channel expression and activity. Journal of Physiology , 594 (20) pp. 5861-5867. 10.1113/JP270675. Green open access

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Abstract

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 (Kv3.1 & Kv4.2) 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 Slack channel. FMRP was also shown to interact with the auxiliary 4 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, Cav2.2, 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.

Type: Article
Title: Fragile X mental retardation protein controls ion channel expression and activity
Location: UK
Open access status: An open access version is available from UCL Discovery
DOI: 10.1113/JP270675
Publisher version: http://dx.doi.org/10.1113/JP270675
Language: English
Additional information: © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society. This is the peer reviewed version of the following article: Ferron, L; (2016) Fragile X Mental Retardation Protein Controls Ion Channel Expression and Activity. Journal of Physiology , 594 (20) pp. 5861-5867, which has been published in final form at http://dx.doi.org/10.1113/JP270675. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Keywords: Fragile X syndrome, Synaptic transmission, Ion channels, Neuronal excitability
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1473296
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