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| Item Type: | Article |
|---|---|
| Title: | Selective transport of neurotransmitters and modulators by distinct volume-regulated LRRC8 anion channels |
| Creators Name: | Lutter, D., Ullrich, F., Lueck, J.C., Kempa, S. and Jentsch, T.J. |
| Abstract: | In response to swelling, mammalian cells release chloride and organic osmolytes through VRAC volume-regulated anion channels. VRACs are heteromers of LRRC8A and other LRRC8 isoforms (B-E) 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 osmolytes taurine and myo-inositol, LRRC8 channels transport the neurotransmitters glutamate, aspartate and GABA and the co-activator D-serine. HEK293 cells engineered to express defined subsets of LRRC8 isoforms were used to elucidate the subunit-dependence of transport. Whereas LRRC8D was crucial for the translocation of overall neutral compounds like myo-inositol, taurine and GABA and sustained the transport of positively charged lysine, flux of negatively charged aspartate was equally well supported by LRRC8E. Disruption of LRRC8B or LRRC8C failed to decrease transport rates of all investigated substrates, but their inclusion into LRRC8 heteromers influenced VRAC's substrate preference. This suggested that individual VRACs can contain three or more different LRRC8 subunits, a conclusion confirmed by sequential co-immunoprecipitations. Our work suggests a composition-dependent role of VRACs in extracellular signal transduction. |
| Keywords: | VSOAC, VSOR, Swelling-Activated Chloride Channel, I(Cl,Vol), I(Cl,Swell), Gliotransmission |
| Source: | Journal of Cell Science |
| ISSN: | 0021-9533 |
| Publisher: | Company of Biologists |
| Volume: | 130 |
| Number: | 6 |
| Page Range: | 1122-1133 |
| Date: | 15 March 2017 |
| Additional Information: | Copyright © 2017 The Authors. Published by The Company of Biologists Ltd. |
| Official Publication: | https://doi.org/10.1242/jcs.196253 |
| PubMed: | View item in PubMed |
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