Journal
SCIENCE
Volume 353, Issue 6294, Pages 83-86Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aaf8411
Keywords
-
Categories
Funding
- NIH [T32 GM008224, GM008281, R01 NS083660, R01 GM029169]
- Pew Scholar Award in Biomedical Sciences
- Schaefer Research Scholar Award
- Klingenstein Fellowship Award in the Neurosciences
- Irma T. Hirschl Career Scientist Award
- Howard Hughes Medical Institute
Ask authors/readers for more resources
AMPA-subtype ionotropic glutamate receptors (AMPARs) mediate fast excitatory neurotransmission and contribute to high cognitive processes such as learning and memory. In the brain, AMPAR trafficking, gating, and pharmacology is tightly controlled by transmembrane AMPAR regulatory proteins (TARPs). Here, we used cryo-electron microscopy to elucidate the structural basis of AMPAR regulation by one of these auxiliary proteins, TARP gamma 2, or stargazin (STZ). Our structures illuminate the variable interaction stoichiometry of the AMPAR-TARP complex, with one or two TARP molecules binding one tetrameric AMPAR. Analysis of the AMPAR-STZ binding interfaces suggests that electrostatic interactions between the extracellular domains of AMPAR and STZ play an important role in modulating AMPAR function through contact surfaces that are conserved across AMPARs and TARPs. We propose a model explaining how TARPs stabilize the activated state of AMPARs and how the interactions between AMPARs and their auxiliary proteins control fast excitatory synaptic transmission.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available