|
KMID : 0892920190280020183
|
|
Experimental Neurobiology
2019 Volume.28 No. 2 p.183 ~ p.215
|
|
|
Tweety-homolog (Ttyh) Family Encodes the Pore-forming Subunits of the Swelling-dependent Volume-regulated Anion Channel (VRACswell) in the Brain
|
|
Han Young-Eun
Kwon Jea
Won Joung-Ha
An Hee-Young
Jang Min-Woo
Woo Jun-Sung
Lee Je-Sun
Park Min-Gu
Yoon Bo-Eun
Lee Seung-Eun
Hwang Eun-Mi
Jung Jae-Young
Park Hyung-Ju
Oh Soo-Jin
Lee C. Justin
|
|
|
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 (VRACswell) remains unclear. Here we identify and characterize Tweety-homologs (TTYH1, TTYH2, TTYH3) as the major VRACswell in astrocytes. Gene-silencing of all Ttyh1/2/3 eliminated hypo-osmotic-solution-induced Cl? conductance (ICl,swell) in cultured and hippocampal astrocytes. When heterologously expressed in HEK293T or CHO-K1 cells, each TTYH isoform showed a significant ICl,swell with similar aquaporin-4 dependency, pharmacological properties and glutamate permeability as ICl,swell observed in native astrocytes. 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 VRACswell in the brain.
|
|
|
KEYWORD
|
|
|
Volume-regulated anion channel, VRAC, Tweety-homolog, Ttyh, Volume regulation
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
  
|