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@ARTICLE{Guzman:838399,
author = {Guzman, Raul and Franzen, Arne and Bungert, Stefanie and
Fahlke, Christoph},
title = {{P}referential {A}ssociation with {C}l{C}-3 {P}ermits
{S}orting of {C}l{C}-4 into {E}ndosomal {C}ompartments},
journal = {The journal of biological chemistry},
volume = {292},
issn = {1083-351X},
address = {Bethesda, Md.},
publisher = {Soc.},
reportid = {FZJ-2017-07011},
pages = {19055-19065},
year = {2017},
abstract = {ClC-4 is an intracellular Cl--H+ exchanger, which is highly
expressed in the brain and whose dysfunction has been linked
to intellectual disability and epilepsy. We here studied the
subcellular localization of human ClC-4 in heterologous
expression systems. ClC-4 is retained in the endoplasmic
reticulum (ER) upon overexpression in HEK293T cells.
Co-expression with distinct ClC-3 splice variants targets
ClC-4 to late endosome/lysosomes (ClC-3a and ClC-3b),
recycling endosome (ClC-3c) or to the Golgi (ClC-3e). When
expressed in cultured astroctyes ClC-4 sorts to endocytic
compartments in WT cells, but was retained in the ER in
Clcn3-/- cells. To understand the virtual absence of ER
localized ClC-4 in WT cells we performed association studies
by high resolution clear native gel electrophoresis (hrCNE).
Whereas other CLCm channels and transporters form stable
dimers, ClC-4 was mostly observed as monomer, with
ClC-3-ClC-4 heterodimers being more stable than ClC-4
homodimers. We conclude that unique oligomerization
properties of ClC-4 permits regulated targeting of ClC-4 to
various endosomal compartments system via expression of
different ClC-3 splice variants.},
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:28972156},
UT = {WOS:000415848000028},
doi = {10.1074/jbc.M117.801951},
url = {https://juser.fz-juelich.de/record/838399},
}