%0 Journal Article
%A Guzman, Raul
%A Franzen, Arne
%A Bungert, Stefanie
%A Fahlke, Christoph
%T Preferential Association with ClC-3 Permits Sorting of ClC-4 into Endosomal Compartments
%J The journal of biological chemistry
%V 292
%@ 1083-351X
%C Bethesda, Md.
%I Soc.
%M FZJ-2017-07011
%P 19055-19065
%D 2017
%X 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.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:28972156
%U <Go to ISI:>//WOS:000415848000028
%R 10.1074/jbc.M117.801951
%U https://juser.fz-juelich.de/record/838399