TY - JOUR
T1 - The transmembrane domain mediates tetramerization of α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors
AU - Gan, Quan
AU - Dai, Jian
AU - Zhou, Huan Xiang
AU - Wollmuth, Lonnie P.
N1 - Publisher Copyright:
©2016 by The American Society for Biochemistry and Molecular Biology, Inc.
PY - 2016/3/18
Y1 - 2016/3/18
N2 - AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the central nervous system. Functional AMPARsare tetrameric complexes with a highly modular structure, consisting of four evolutionarily distinct structural domains: An amino-terminal domain (ATD), a ligand-binding domain (LBD), a channel-forming transmembrane domain (TMD), and a carboxyl-terminal domain (CTD). Here we show that the isolated TMD of the GluA1 AMPAR is fully capable of tetramerization. Additionally, removal of the extracellular domains from the receptor did not affect membrane topology or surface delivery. Furthermore, whereas the ATD and CTD contribute positively to tetramerization, the LBD presents a barrier to the process by reducing the stability of the receptor complex. These experiments pinpoint the TMD as the "tetramerization domain" for AMPARs, with other domains playing modulatory roles. They also raise intriguing questions about the evolution of iGluRs as well as the mechanisms regulating the biogenesis of AMPAR complexes.
AB - AMPA receptors (AMPARs) mediate fast excitatory neurotransmission in the central nervous system. Functional AMPARsare tetrameric complexes with a highly modular structure, consisting of four evolutionarily distinct structural domains: An amino-terminal domain (ATD), a ligand-binding domain (LBD), a channel-forming transmembrane domain (TMD), and a carboxyl-terminal domain (CTD). Here we show that the isolated TMD of the GluA1 AMPAR is fully capable of tetramerization. Additionally, removal of the extracellular domains from the receptor did not affect membrane topology or surface delivery. Furthermore, whereas the ATD and CTD contribute positively to tetramerization, the LBD presents a barrier to the process by reducing the stability of the receptor complex. These experiments pinpoint the TMD as the "tetramerization domain" for AMPARs, with other domains playing modulatory roles. They also raise intriguing questions about the evolution of iGluRs as well as the mechanisms regulating the biogenesis of AMPAR complexes.
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U2 - 10.1074/jbc.M115.686246
DO - 10.1074/jbc.M115.686246
M3 - Article
C2 - 26839312
AN - SCOPUS:84964888489
SN - 0021-9258
VL - 291
SP - 6595
EP - 6606
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 12
ER -