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@ARTICLE{Steinke:202863,
author = {Steinke, Kim Vanessa and Gorinski, Nataliya and
Wojciechowski, Daniel and Todorov, Vladimir and Guseva,
Daria and Ponimaskin, Evgeni and Fahlke, Christoph and
Fischer, Martin},
title = {{H}uman {CLC}-{K} {C}hannels {R}equire {P}almitoylation of
{T}heir {A}ccessory {S}ubunit {B}arttin to {B}e
{F}unctional.},
journal = {The journal of biological chemistry},
volume = {290},
number = {28},
issn = {1083-351X},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {FZJ-2015-05015},
pages = {17390 - 17400},
year = {2015},
abstract = {CLC-K/barttin chloride channels are essential for NaCl
re-absorption in Henle's loop and for potassium secretion by
the stria vascularis in the inner ear. Here, we studied the
posttranslational modification of such channels by
palmitoylation of their accessory subunit barttin. We found
that barttin is palmitoylated in vivo and in vitro and
identified two conserved cysteine residues at positions 54
and 56 as palmitoylation sites. Point mutations at these two
residues reduce the macroscopic current amplitudes in cells
expressing CLC-K/barttin channels proportionally to the
relative reduction in palmitoylated barttin. CLC-K/barttin
expression, plasma membrane insertion, and single channel
properties remain unaffected, indicating that these
mutations decrease the number of active channels. R8W and
G47R, two naturally occurring barttin mutations identified
in patients with Bartter syndrome type IV, reduce barttin
palmitoylation and CLC-K/barttin channel activity.
Palmitoylation of the accessory subunit barttin might thus
play a role in chloride channel dysfunction in certain
variants of Bartter syndrome. We did not observe pronounced
alteration of barttin palmitoylation upon increased salt and
water intake or water deprivation, indicating that this
posttranslational modification does not contribute to long
term adaptation to variable water intake. Our results
identify barttin palmitoylation as a novel posttranslational
modification of CLC-K/barttin chloride channels.},
cin = {ICS-4},
ddc = {570},
cid = {I:(DE-Juel1)ICS-4-20110106},
pnm = {552 - Engineering Cell Function (POF3-552)},
pid = {G:(DE-HGF)POF3-552},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:26013830},
pmc = {pmc:PMC4498076},
UT = {WOS:000357730900033},
doi = {10.1074/jbc.M114.631705},
url = {https://juser.fz-juelich.de/record/202863},
}