Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels

Abstract Recombinant TWIK2 channels produce weak basal background K+ currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking....

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Autores principales:	Nicole Bobak, Sylvain Feliciangeli, Cheng-Chang Chen, Ismail Ben Soussia, Stefan Bittner, Sophie Pagnotta, Tobias Ruck, Martin Biel, Christian Wahl-Schott, Christian Grimm, Sven G. Meuth, Florian Lesage
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c08363747f7a45328c794c87466f64ca
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spelling	oai:doaj.org-article:c08363747f7a45328c794c87466f64ca2021-12-02T16:07:44ZRecombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels10.1038/s41598-017-00640-82045-2322https://doaj.org/article/c08363747f7a45328c794c87466f64ca2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00640-8https://doaj.org/toc/2045-2322Abstract Recombinant TWIK2 channels produce weak basal background K+ currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane. In addition, TWIK2 contains two N-glycosylation sites (N79AS and N85AS) on its luminal side, and glycosylation is necessary for expression in lysosomes. As shown by electrophysiology and electron microscopy, TWIK2 produces functional background K+ currents in the endolysosomes, and its expression affects the number and mean size of the lysosomes. These results show that TWIK2 is expressed in lysosomes, further expanding the registry of ion channels expressed in these organelles.Nicole BobakSylvain FeliciangeliCheng-Chang ChenIsmail Ben SoussiaStefan BittnerSophie PagnottaTobias RuckMartin BielChristian Wahl-SchottChristian GrimmSven G. MeuthFlorian LesageNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nicole Bobak Sylvain Feliciangeli Cheng-Chang Chen Ismail Ben Soussia Stefan Bittner Sophie Pagnotta Tobias Ruck Martin Biel Christian Wahl-Schott Christian Grimm Sven G. Meuth Florian Lesage Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
description	Abstract Recombinant TWIK2 channels produce weak basal background K+ currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane. In addition, TWIK2 contains two N-glycosylation sites (N79AS and N85AS) on its luminal side, and glycosylation is necessary for expression in lysosomes. As shown by electrophysiology and electron microscopy, TWIK2 produces functional background K+ currents in the endolysosomes, and its expression affects the number and mean size of the lysosomes. These results show that TWIK2 is expressed in lysosomes, further expanding the registry of ion channels expressed in these organelles.
format	article
author	Nicole Bobak Sylvain Feliciangeli Cheng-Chang Chen Ismail Ben Soussia Stefan Bittner Sophie Pagnotta Tobias Ruck Martin Biel Christian Wahl-Schott Christian Grimm Sven G. Meuth Florian Lesage
author_facet	Nicole Bobak Sylvain Feliciangeli Cheng-Chang Chen Ismail Ben Soussia Stefan Bittner Sophie Pagnotta Tobias Ruck Martin Biel Christian Wahl-Schott Christian Grimm Sven G. Meuth Florian Lesage
author_sort	Nicole Bobak
title	Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
title_short	Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
title_full	Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
title_fullStr	Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
title_full_unstemmed	Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels
title_sort	recombinant tandem of pore-domains in a weakly inward rectifying k+ channel 2 (twik2) forms active lysosomal channels
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c08363747f7a45328c794c87466f64ca
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Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels

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