Presentation Abstract

Program#/Poster#: 429.16/B33
Presentation Title: Differences of AMPA and kainate receptor interactomes identify a novel AMPA receptor auxiliary subunit, GSG1L
Location: Hall F-J
Presentation time: Monday, Oct 15, 2012, 4:00 PM - 5:00 PM
Authors: *T. NAKAGAWA1, N. F. SHANKS2, J. N. SAVAS4, T. MARUO1, O. CAIS5, A. HIRAO6, S. OE6, A. GHOSH3, Y. NODA6, I. H. GREGER5, J. R. YATES, III4;
1Chem and Biochem, 2Neurosciences Grad. Program, 3Div. of Biol. and Section of Neurosci., UCSD, LA JOLLA, CA; 4Chem. Physiol., Scripps Res. Inst., La Jolla, CA; 5Neurobio., MRC Lab. of Mol. Biol., Cambridge, United Kingdom; 6Anat., Jichi Med. Univ., Tochigi, Japan
Abstract: Glutamate receptor complexes are extensively studied, yet new binding proteins are continuously reported. In this study, we wished to identify new interactors, so we compared the interactomes of native AMPA and kainate receptors. To do this, we performed immuno-affinity purification of the native receptors from rat brain followed by shotgun LC-MS/MS protein analysis (AP-MS/MS). The co-purifying proteins were directly analyzed by multidimensional protein identification technology (MudPIT). In this way, we identified the majority of known interacting proteins and, more importantly, the outcome provides novel candidates for further studies. Among the candidates, we focused on a predicted protein GSG1L, a membrane protein that co-purified specifically with AMPA-Rs. GSG1L is a distant homologue of stg/TARPs that belongs to the extended claudin family. Using detailed molecular, cellular, electrophysiological, and biochemical experiments, we validated the interaction and determined that GSG1L is unique modulator of AMPA-R channel function. We suggest that GSG1L is a novel AMPA-R auxiliary subunit that extends the repertoire of AMPA-R function. This study provides a proof-of-principal for identifying novel interactors, and further investigation of other candidates may reveal additional complexity of ionotropic glutamate receptor function.
Disclosures:  T. Nakagawa: None. N.F. Shanks: None. J.N. Savas: None. T. Maruo: None. O. Cais: None. A. Hirao: None. S. Oe: None. A. Ghosh: None. Y. Noda: None. I.H. Greger: None. J.R. Yates: None.
Keyword(s): AMPA RECEPTOR
Support: NIH R01HD061543
[Authors]. [Abstract Title]. Program No. XXX.XX. 2012 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2012. Online.

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