PT  - JOURNAL ARTICLE
AU  - Natalie F. Shanks
AU  - Tomohiko Maruo
AU  - Anthony N. Farina
AU  - Mark H. Ellisman
AU  - Terunaga Nakagawa
TI  - Contribution of the Global Subunit Structure and Stargazin on the Maturation of AMPA Receptors
AID  - 10.1523/JNEUROSCI.5146-09.2010
DP  - 2010 Feb 17
TA  - The Journal of Neuroscience
PG  - 2728--2740
VI  - 30
IP  - 7
4099  - http://www.jneurosci.org/content/30/7/2728.short
4100  - http://www.jneurosci.org/content/30/7/2728.full
SO  - J. Neurosci.2010 Feb 17; 30
AB  - Subunit assembly governs regulation of AMPA receptor (AMPA-R) synaptic delivery and determines biophysical parameters of the ion channel. However, little is known about the molecular pathways of this process. Here, we present single-particle EM three-dimensional structures of dimeric biosynthetic intermediates of the GluA2 subunit of AMPA-Rs. Consistent with the structures of intact tetramers, the N-terminal domains of the biosynthetic intermediates form dimers. Transmembrane domains also dimerize despite the two ligand-binding domains (LBDs) being separated. A significant difference was detected between the dimeric structures of the wild type and the L504Y mutant, a point mutation that blocks receptor trafficking and desensitization. In contrast to the wild type, whose LBD is separated, the LBD of the L504Y mutant was detected as a single density. Our results provide direct structural evidence that separation of the LBD within the intact dimeric subunits is critical for efficient tetramerization in the endoplasmic reticulum and further trafficking of AMPA-Rs. The contribution of stargazin on the subunit assembly of AMPA-R was examined. Our data suggest that stargazin affects AMPA-R trafficking at a later stage of receptor maturation.