LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength
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چکیده
منابع مشابه
LRRC8 Proteins Form Volume-Regulated Anion Channels that Sense Ionic Strength
The volume-regulated anion channel (VRAC) is activated when a cell swells, and it plays a central role in maintaining cell volume in response to osmotic challenges. SWELL1 (LRRC8A) was recently identified as an essential component of VRAC. However, the identity of the pore-forming subunits of VRAC and how the channel is gated by cell swelling are unknown. Here, we show that SWELL1 and up to fou...
متن کاملSelective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels.
In response to swelling, mammalian cells release chloride and organic osmolytes through volume-regulated anion channels (VRACs). VRACs are heteromers of LRRC8A and other LRRC8 isoforms (LRRC8B to LRRC8E), which are co-expressed in HEK293 and most other cells. The spectrum of VRAC substrates and its dependence on particular LRRC8 isoforms remains largely unknown. We show that, besides the osmoly...
متن کاملIdentification of LRRC8 heteromers as an essential component of the volume-regulated anion channel VRAC.
Regulation of cell volume is critical for many cellular and organismal functions, yet the molecular identity of a key player, the volume-regulated anion channel VRAC, has remained unknown. A genome-wide small interfering RNA screen in mammalian cells identified LRRC8A as a VRAC component. LRRC8A formed heteromers with other LRRC8 multispan membrane proteins. Genomic disruption of LRRC8A ablated...
متن کاملIntracellular ionic strength regulates the volume sensitivity of a swelling-activated anion channel.
Cell swelling activates an outwardly rectifying anion channel termed VSOAC (volume-sensitive organic osmolyte/anion channel). Regulation of VSOAC by intracellular electrolytes was characterized in Chinese hamster ovary cells by whole cell patch clamp. Elevation of intracellular CsCl concentration from 40 to 180 mM resulted in a concentration-dependent decrease in channel activation. Activation ...
متن کاملLRRC8 proteins share a common ancestor with pannexins, and may form hexameric channels involved in cell-cell communication.
Leucine-rich repeat-containing 8 (LRRC8) proteins are composed of four transmembrane helices and 17 leucine-rich repeats (LRR). Although LRRC8 proteins have been associated with important processes, like maturation of B cells or adipocyte differentiation, their biology and molecular function are largely unknown. We found that LRRC8 proteins originated from the combination of a pannexin and an L...
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ژورنال
عنوان ژورنال: Cell
سال: 2016
ISSN: 0092-8674
DOI: 10.1016/j.cell.2015.12.031