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인지 및 사회성 연구단
인지 및 사회성 연구단
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Tweety-homolog (Ttyh) Family Encodes the Pore-forming Subunits of the Swelling-dependent Volume-regulated Anion Channel (VRAC(swell)) in the Brain

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Title
Tweety-homolog (Ttyh) Family Encodes the Pore-forming Subunits of the Swelling-dependent Volume-regulated Anion Channel (VRAC(swell)) in the Brain
Author(s)
Young-Eun Han; Jea Kwon; Joungha Won; Heeyoung An; Minwoo Wendy Jang; Woo, J; Lee, JS; Min Gu Park; Yoon, BE; Lee, SE; Hwang, EM; Jung, JY; Park, H; Oh, SJ; C. Justin Lee
Publication Date
2019-04
Journal
EXPERIMENTAL NEUROBIOLOGY, v.28, no.2, pp.183 - 215
Publisher
KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
Abstract
In the brain, a reduction in extracellular osmolality causes water-influx and swelling, which subsequently triggers Cl - and osmolytes-efflux via volume-regulated anion channel (VRAC). Although LRRC8 family has been recently proposed as the pore-forming VRAC which is activated by low cytoplasmic ionic strength but not by swelling, the molecular identity of the pore-forming swelling-dependent VRAC (VRAC(swell)) remains unclear. Here we identify and characterize. Tweety- homologs (TTYH1, TTYH2, TTYH3) as the major VRAC(swell) in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl- conductance (I-Cl,I-swell) in cultured and hippocainpal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH iso-form showed a significant I-Cl,I-swell with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as I-Cl,I-swell observed in native astrocres. Mutagenesis-based structure-activity analysis revealed that positively charged arginine residue at 165 in TTYH1 and 164 in TTYH2 is critical for the formation of the channel-pore. Our results demonstrate that TTYH family confers the bona fide VRAC(swell) in the brain. © Experimental Neurobiology 2019.
URI
https://pr.ibs.re.kr/handle/8788114/6933
ISSN
1226-2560
Appears in Collections:
Center for Cognition and Sociality(인지 및 사회성 연구단) > Cognitive Glioscience Group(인지 교세포과학 그룹) > Journal Papers (저널논문)
Center for Cognition and Sociality(인지 및 사회성 연구단) > Journal Papers (저널논문)
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