Two Nedd4-binding Motifs Underlie Modulation of Sodium Channel Nav1.6 by p38 MAPK

Gasser, Andreas; Cheng, Xiaoyang; Gilmore, Elaine S.; Tyrrell, Lynda; Waxman, Stephen G.; Dib‐Hajj, Sulayman D.

doi:10.1074/jbc.m109.098681

Cited by 49 publications

(54 citation statements)

References 49 publications

(37 reference statements)

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“…hNa V 1.6R (WT) and hNa V 1.6-M136V (called Met136Val hereafter) were cotransfected with enhanced green fluorescent protein (EGFP) constructs into ND7/23 cells as previously described (21)(22)(23). Briefly, cells were plated at low density on 10 mm coverslips in 24-well plates and incubated at 37°C for 24 h before transfection.…”

Section: Plasmid and Animalsmentioning

confidence: 99%

“…ND7/23 cells with robust green fluorescence and WT or Met136Val were recorded on the same day under similar conditions (21)(22)(23). Whole-cell voltage -clamp recordings were performed using an EPC10-double amplifier and Patchmaster software (HEKA Electronik) at RT (20° ± 1°C).…”

Section: In a Case Of Trigeminal Neuralgiamentioning

confidence: 99%

“…The extracellular solution contained (in mM): 140 NaCl, 3 KCl, 1 MgCl 2 , 1 CaCl 2 , 10 N-2-hydroxyethylpiperazine-N′-2-ethanesulfonic acid (HEPES), 5 CsCl, 20 TEA-Cl, 0.1 CdCl 2 , pH 7.3 with NaOH (osmolarity adjusted to 320 mOsm with sucrose). Tetrodotoxin (TTX) (500 nM) was added to the bath to block endogenous TTX-sensitive sodium currents in ND7/23 cells (21)(22)(23). Patch pipettes were fabricated from borosilicate glass (1.65/1.1, OD/ID; World Precision Instruments) using a Sutter Instruments P-97 puller and had a resistance of 0.8-1.5 MΩ.…”

Section: In a Case Of Trigeminal Neuralgiamentioning

confidence: 99%

See 2 more Smart Citations

A Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia

Tanaka¹,

Zhao²,

Dib-Hajj³

et al. 2016

Mol Med

101

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Section: Plasmid and Animalsmentioning

confidence: 99%

Section: In a Case Of Trigeminal Neuralgiamentioning

confidence: 99%

Section: In a Case Of Trigeminal Neuralgiamentioning

confidence: 99%

See 1 more Smart Citation

A Gain-of-Function Mutation in Nav1.6 in a Case of Trigeminal Neuralgia

Tanaka¹,

Zhao²,

Dib-Hajj³

et al. 2016

Mol Med

101

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“…Much like ENaC, cell surface stability of the cardiac Na v 1.5 was demonstrated to be negatively regulated by Nedd4-2, a process that requires the PY motif of this channel, as well as active Nedd4-2, suggesting channel ubiquitylation regulates its endocytosis [1,204] Recently it was shown that Nav1.6 is regulated by Nedd4-2 as well. Interestingly Nedd4-2 appears to interact with 2 motifs, one of which is a PGSP motif that needs to be phosphorylated by the p38 kinase in order to interact with Nedd4-2 [66].…”

Section: Regulation Of Endocytosis Of Other Ion Channels By Nedd4 Fammentioning

confidence: 99%

Role of the ubiquitin system in regulating ion transport

Rotin

Staub

2010

Pflugers Arch - Eur J Physiol

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Ion channels and transporters play a critical role in ion and fluid homeostasis and thus in normal animal physiology and pathology. Tight regulation of these transmembrane proteins is therefore essential. In recent years, many studies have focused their attention on the role of the ubiquitin system in regulating ion channels and transporters, initialed by the discoveries of the role of this system in processing of Cystic Fibrosis Transmembrane Regulator (CFTR), and in regulating endocytosis of the epithelial Na + channel (ENaC) by the Nedd4 family of ubiquitin ligases (mainly Nedd4-2). In this review, we discuss the role of the ubiquitin system in ER Associated Degradation (ERAD) of ion channels, and in the regulation of endocytosis and lysosomal sorting of ion channels and transporters, focusing primarily in mammalian cells. We also briefly discuss the role of ubiquitin like molecules (such as SUMO) in such regulation, for which much less is known so far.

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“…Previous studies have shown sequences that are similar but not identical, such as LPTY can bind to Nedd4-2. 92 The binding motif of KCNQ2 and 3 subunits that is recognized by Nedd4-2 remains to be elucidated. Similarly, for K V 1.3 channels that does not contain a PY motif, Nedd4-2 is able to reduce peak K + current amplitude by >50% in Xenopus oocytes.…”

confidence: 99%