TY  - JOUR
AU  - Guzman, Raul
AU  - Franzen, Arne
AU  - Bungert, Stefanie
AU  - Fahlke, Christoph
TI  - Preferential Association with ClC-3 Permits Sorting of ClC-4 into Endosomal Compartments
JO  - The journal of biological chemistry
VL  - 292
SN  - 1083-351X
CY  - Bethesda, Md.
PB  - Soc.
M1  - FZJ-2017-07011
SP  - 19055-19065
PY  - 2017
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:28972156
UR  - <Go to ISI:>//WOS:000415848000028
DO  - DOI:10.1074/jbc.M117.801951
UR  - https://juser.fz-juelich.de/record/838399
ER  -