LRRC8E Membrane Protein Introduction

Introduction of LRRC8E

LRRC8E, also known as Leucine-rich repeat-containing protein 8E, is a protein encoded by the human LRRC8E gene. Volume-regulated anion channels (VRAC) is a ubiquitous channel that is normally open in response to cell swelling or any other manipulation that dilutes cellular ion content. VRAC is known for its pivotal role in cell homeostasis, but it also involves in cellular processes, including regulation of membrane potential, emitter release and cell proliferation. Early studies have shown that VRAC has a functional role in cisplatin-induced cell death. The LRRC8 protein forms a small family of intact membrane proteins with four transmembrane helices and includes five homologs (LRRC8A-E) in mammals and most other chord animals. Current evidence indicates that the functional VRAC channel is a heteromultimer containing the necessary LRRC8A subunit supplemented by at least one other four isoforms.

Function of LRRC8E Membrane Protein

The volume-regulated anion channels (VRAC) play an important role in cell volume regulation in various cell types. Volume-regulated anion channel is an important component of the cellular response to osmotic swelling. This process occurs when aquaporin-mediated water flows into the cell under hypotonic conditions. To counteract the increase in cell volume and prevent rupture caused by swelling, different ion transporters are activated to control the flow of ions, organic permeate and water, and returns to the cells to maintain their original normal state. Proteins involved in this regulated volume reduction include selective ion channels, secondary active transporters, and VRAC. Additionally, VRAC appears to contribute importantly to a wide range of other cellular functions and pathological events, including cell motility, cell proliferation, apoptosis and electrical excitability of neurons by releasing neurotransmitters from astrocytes.

Fig.1 The anticancer drugs cisplatin and carboplatin as well as the pro-apoptotic staurosporine enter the cell by passive diffusion. Pt-based drugs induce non-apoptotic cell death by DNA damage and induce apoptosis to a lesser extent, while Pt-based drugs and staurosporine channels containing LRRC8A and LRRC8D are mainly used uptake of Pt-based drugs.

Application of LRRC8E Membrane Protein in Literature

1. Gaitán-Peñas H., et al. Investigation of LRRC8-Mediated Volume-Regulated Anion Currents in Xenopus Oocytes. Biophysical Journal. 2016, 111(7):1429-1443. PubMed ID: 27705766
   
   

   This article suggests that LRRC8 heteromers mediate anion and osmolyte flux with subunit-dependent kinetics and selectivity. Additionally, it finds that LRRC8 heteromers can mediate glutamate and ATP flux.

2. Yamada T., et al. Intracellular and extracellular loops of LRRC8 are essential for volume-regulated anion channel function. Journal of general physiology. 2018, 150(7):1003-1015. PubMed ID: 29853476
   
   

   This paper demonstrates that LRRC8A IL and EL1 of LRRC8C, LRRC8D, or LRRC8E are critical for the formation and function of VRACs and provides new insights into channel structure and regulation.

3. Lück J.C., et al. LRRC8/VRAC anion channels are required for late stages of spermatid development in mice. Journal of Biological Chemistry. 2018, 293(30):11796-11808. PubMed ID: 29880644
   
   

   This paper shows that VRAC may perform correct sperm development in a cell-autonomous manner through its role in cell volume regulation and explains the male infertility of Lrrc8a^-/- mice and the spontaneous mouse mutant ébouriffé.

4. Syeda R., et al. LRRC8 proteins form volume-regulated anion channels that sense ionic strength. Cell. 2016, 164(3):499-511. PubMed ID: 26824658
   
   

   This article demonstrates that LRRC8 proteins constitute the VRAC pore and hypotonic stress can activate VRAC through a decrease in the cytoplasmic.

5. Mongin A.A. Volume-regulated anion channel-a frenemy within the brain. Pflügers Archiv-European Journal of Physiology. 2016, 468(3):421-41. PubMed ID: 26620797
   
   

   This review provides a brief overview of the central nervous system, with a focus on the expected impact of LRRC8 findings on the further development of neuroscience research.

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