Structural and compositional diversity in the kainate receptor family.
Autor: | Selvakumar P; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA., Lee J; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA., Khanra N; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA., He C; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA., Munguba H; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA., Kiese L; Department of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany., Broichhagen J; Leibniz-Forschungsinstitut für Molekulare Pharmakologie, 13125 Berlin, Germany., Reiner A; Department of Biology and Biotechnology, Ruhr University Bochum, Bochum, Germany., Levitz J; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: jtl2003@med.cornell.edu., Meyerson JR; Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA. Electronic address: jrm2008@med.cornell.edu. |
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Jazyk: | angličtina |
Zdroj: | Cell reports [Cell Rep] 2021 Oct 26; Vol. 37 (4), pp. 109891. |
DOI: | 10.1016/j.celrep.2021.109891 |
Abstrakt: | The kainate receptors (KARs) are members of the ionotropic glutamate receptor family and assemble into tetramers from a pool of five subunit types (GluK1-5). Each subunit confers distinct functional properties to a receptor, but the compositional and stoichiometric diversity of KAR tetramers is not well understood. To address this, we first solve the structure of the GluK1 homomer, which enables a systematic assessment of structural compatibility among KAR subunits. Next, we analyze single-cell RNA sequencing data, which reveal extreme diversity in the combinations of two or more KAR subunits co-expressed within the same cell. We then investigate the composition of individual receptor complexes using single-molecule fluorescence techniques and find that di-heteromers assembled from GluK1, GluK2, or GluK3 can form with all possible stoichiometries, while GluK1/K5, GluK2/K5, and GluK3/K5 can form 3:1 or 2:2 complexes. Finally, using three-color single-molecule imaging, we discover that KARs can form tri- and tetra-heteromers. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) |
Databáze: | MEDLINE |
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