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PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1

Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel K(V)10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tum...

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Autores principales: Herrmann, Solveig, Ninkovic, Milena, Kohl, Tobias, Pardo, Luis A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743135/
https://www.ncbi.nlm.nih.gov/pubmed/23966943
http://dx.doi.org/10.3389/fphys.2013.00201
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author Herrmann, Solveig
Ninkovic, Milena
Kohl, Tobias
Pardo, Luis A.
author_facet Herrmann, Solveig
Ninkovic, Milena
Kohl, Tobias
Pardo, Luis A.
author_sort Herrmann, Solveig
collection PubMed
description Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel K(V)10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tumors and possible use as a therapeutic target. The Golgi resident protein PIST binds several membrane proteins, thereby modulating their expression. Here we describe a PDZ domain-mediated interaction of K(V)10.1 and PIST, which enhances surface levels of K(V)10.1. The functional, but not the physical interaction of both proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of eight amino acids in the coiled-coil domain to render the neural form of PIST (nPIST) and the corresponding short isoform in an as-of-yet unknown form abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST) lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously expressed. PIST and K(V)10.1 co-precipitate from native and expression systems. nPIST also showed interaction, but did not alter the functional expression of the channel. We could not document physical interaction between K(V)10.1 and sPIST, but it reduced K(V)10.1 functional expression in a dominant-negative manner. nsPIST showed weak physical interaction and no functional effect on K(V)10.1. We propose these isoforms to work as modulators of PIST function via regulating the binding on interaction partners.
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spelling pubmed-37431352013-08-21 PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1 Herrmann, Solveig Ninkovic, Milena Kohl, Tobias Pardo, Luis A. Front Physiol Physiology Although crucial for their correct function, the mechanisms controlling surface expression of ion channels are poorly understood. In the case of the voltage-gated potassium channel K(V)10.1, this is determinant not only for its physiological function in brain, but also for its pathophysiology in tumors and possible use as a therapeutic target. The Golgi resident protein PIST binds several membrane proteins, thereby modulating their expression. Here we describe a PDZ domain-mediated interaction of K(V)10.1 and PIST, which enhances surface levels of K(V)10.1. The functional, but not the physical interaction of both proteins is dependent on the coiled-coil and PDZ domains of PIST; insertion of eight amino acids in the coiled-coil domain to render the neural form of PIST (nPIST) and the corresponding short isoform in an as-of-yet unknown form abolishes the effect. In addition, two new isoforms of PIST (sPIST and nsPIST) lacking nearly the complete PDZ domain were cloned and shown to be ubiquitously expressed. PIST and K(V)10.1 co-precipitate from native and expression systems. nPIST also showed interaction, but did not alter the functional expression of the channel. We could not document physical interaction between K(V)10.1 and sPIST, but it reduced K(V)10.1 functional expression in a dominant-negative manner. nsPIST showed weak physical interaction and no functional effect on K(V)10.1. We propose these isoforms to work as modulators of PIST function via regulating the binding on interaction partners. Frontiers Media S.A. 2013-08-14 /pmc/articles/PMC3743135/ /pubmed/23966943 http://dx.doi.org/10.3389/fphys.2013.00201 Text en Copyright © 2013 Herrmann, Ninkovic, Kohl and Pardo. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Physiology
Herrmann, Solveig
Ninkovic, Milena
Kohl, Tobias
Pardo, Luis A.
PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title_full PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title_fullStr PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title_full_unstemmed PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title_short PIST (GOPC) modulates the oncogenic voltage-gated potassium channel K(V)10.1
title_sort pist (gopc) modulates the oncogenic voltage-gated potassium channel k(v)10.1
topic Physiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3743135/
https://www.ncbi.nlm.nih.gov/pubmed/23966943
http://dx.doi.org/10.3389/fphys.2013.00201
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