| First Author | Guzman RE | Year | 2017 |
| Journal | J Biol Chem | Volume | 292 |
| Issue | 46 | Pages | 19055-19065 |
| PubMed ID | 28972156 | Mgi Jnum | J:287033 |
| Mgi Id | MGI:6414690 | Doi | 10.1074/jbc.M117.801951 |
| Citation | Guzman RE, et al. (2017) Preferential association with ClC-3 permits sorting of ClC-4 into endosomal compartments. J Biol Chem 292(46):19055-19065 |
| abstractText | ClC-4 is an intracellular Cl(-)/H(+) exchanger that is highly expressed in the brain and whose dysfunction has been linked to intellectual disability and epilepsy. Here we 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) or recycling endosome (ClC-3c). When expressed in cultured astrocytes, ClC-4 sorted 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 astrocytes, we performed association studies by high-resolution clear native gel electrophoresis. Although other CLC 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 permit regulated targeting of ClC-4 to various endosomal compartment systems via expression of different ClC-3 splice variants. |
