NDLI: Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes

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Structural Bases of Desensitization in AMPA Receptor-Auxiliary Subunit Complexes

Content Provider	Semantic Scholar
Author	Twomey, Edward C. Yelshanskaya, Maria V. Grassucci, Robert A. Frank, Joachim Sobolevsky, Alexander I.
Copyright Year	2017
Abstract	Fast excitatory neurotransmission is mediated by AMPA-subtype ionotropic glutamate receptors (AMPARs). AMPARs, localized at post-synaptic densities, are regulated by transmembrane auxiliary subunits that modulate AMPAR assembly, trafficking, gating, and pharmacology. Aberrancies in AMPAR-mediated signaling are associated with numerous neurological disorders. Here, we report cryo-EM structures of an AMPAR in complex with the auxiliary subunit GSG1L in the closed and desensitized states. GSG1L favors the AMPAR desensitized state, where channel closure is facilitated by profound structural rearrangements in the AMPAR extracellular domain, with ligand-binding domain dimers losing their local 2-fold rotational symmetry. Our structural and functional experiments suggest that AMPAR auxiliary subunits share a modular architecture and use a common transmembrane scaffold for distinct extracellular modules to differentially regulate AMPAR gating. By comparing the AMPAR-GSG1L complex structures, we map conformational changes accompanying AMPAR recovery from desensitization and reveal structural bases for regulation of synaptic transmission by auxiliary subunits.
Starting Page	174
Ending Page	187
Page Count	14
File Format	PDF HTM / HTML
DOI	10.1016/j.neuron.2017.04.025
PubMed reference number	28472657
Journal	Medline
Volume Number	94
Alternate Webpage(s)	http://anatomy.med.wayne.edu/pdfs/structure_bases_of_ampa_desensitization_twomey_et_al_neuron_2017.pdf
Alternate Webpage(s)	https://api.elsevier.com/content/article/pii/S0896627317303513
Alternate Webpage(s)	https://www.sciencedirect.com/science/article/pii/S0896627317303513
Alternate Webpage(s)	https://doi.org/10.1016/j.neuron.2017.04.025
Journal	Neuron
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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