Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor

Beatriz Herguedas, Bianka K. Kohegyi, Jan-Niklas Dohrke, Jake F. Watson, Danyang Zhang, Hinze Ho, Saher A. Shaikh, Remigijus Lape, James M. Krieger and Ingo H. Greger ()
Additional contact information
Beatriz Herguedas: Neurobiology Division MRC Laboratory of Molecular Biology
Bianka K. Kohegyi: Neurobiology Division MRC Laboratory of Molecular Biology
Jan-Niklas Dohrke: Neurobiology Division MRC Laboratory of Molecular Biology
Jake F. Watson: Neurobiology Division MRC Laboratory of Molecular Biology
Danyang Zhang: Neurobiology Division MRC Laboratory of Molecular Biology
Hinze Ho: Neurobiology Division MRC Laboratory of Molecular Biology
Saher A. Shaikh: Neurobiology Division MRC Laboratory of Molecular Biology
Remigijus Lape: Neurobiology Division MRC Laboratory of Molecular Biology
James M. Krieger: Neurobiology Division MRC Laboratory of Molecular Biology
Ingo H. Greger: Neurobiology Division MRC Laboratory of Molecular Biology

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract AMPA-type glutamate receptors (AMPARs) mediate rapid signal transmission at excitatory synapses in the brain. Glutamate binding to the receptor’s ligand-binding domains (LBDs) leads to ion channel activation and desensitization. Gating kinetics shape synaptic transmission and are strongly modulated by transmembrane AMPAR regulatory proteins (TARPs) through currently incompletely resolved mechanisms. Here, electron cryo-microscopy structures of the GluA1/2 TARP-γ8 complex, in both open and desensitized states (at 3.5 Å), reveal state-selective engagement of the LBDs by the large TARP-γ8 loop (‘β1’), elucidating how this TARP stabilizes specific gating states. We further show how TARPs alter channel rectification, by interacting with the pore helix of the selectivity filter. Lastly, we reveal that the Q/R-editing site couples the channel constriction at the filter entrance to the gate, and forms the major cation binding site in the conduction path. Our results provide a mechanistic framework of how TARPs modulate AMPAR gating and conductance.

Date: 2022
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (2)

Downloads: (external link)
https://www.nature.com/articles/s41467-022-28404-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28404-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-022-28404-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().