LRRC8E
Domain
The volume-regulated anion channel (VRAC) channel forms a trimer of dimers, with symmetry mismatch between the pore-forming domain and the cytosolic LRR repeats, a topology similar to gap junction proteins.
Function
Non-essential component of the volume-regulated anion channel (VRAC, also named VSOAC channel), an anion channel required to maintain a constant cell volume in response to extracellular or intracellular osmotic changes (PubMed:24790029, PubMed:26824658, PubMed:28193731). The VRAC channel conducts iodide better than chloride and can also conduct organic osmolytes like taurine (PubMed:24790029, PubMed:26824658). Mediates efflux of amino acids, such as aspartate, in response to osmotic stress (PubMed:28193731). The VRAC channel also mediates transport of immunoreactive cyclic dinucleotide GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol (PubMed:33171122). Channel activity requires LRRC8A plus at least one other family member (LRRC8B, LRRC8C, LRRC8D or LRRC8E); channel characteristics depend on the precise subunit composition (PubMed:24790029, PubMed:26824658, PubMed:28193731). Also plays a role in lysosome homeostasis by forming functional lysosomal VRAC channels in response to low cytoplasmic ionic strength condition: lysosomal VRAC channels are necessary for the formation of large lysosome-derived vacuoles, which store and then expel excess water to maintain cytosolic water homeostasis (PubMed:33139539).
Sequence Similarities
Belongs to the LRRC8 family.
Cellular localization
- Cell membrane
- Multi-pass membrane protein
- Endoplasmic reticulum membrane
- Lysosome membrane
- Multi-pass membrane protein
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- In the absence of LRRC8A, resides primarily in the endoplasmic reticulum (PubMed:24790029, PubMed:33139539). Requires LRRC8A for localization at the cell membrane or lysosome membrane (PubMed:24790029, PubMed:33139539).
Alternative names
Volume-regulated anion channel subunit LRRC8E, Leucine-rich repeat-containing protein 8E, LRRC8E