High-Resolution Proteomics Unravel Architecture and Molecular Diversity of Native AMPA Receptor Complexes

详细信息	查看全文 | 推荐本文 |

• 作者：Jochen Schwenk¹ ; ⁴ ; ⁵ ; Nadine Harmel³ ; ⁵ ; Aline Brechet¹ ; Gerd Zolles¹ ; Henrike Berkefeld¹ ; Catrin  ; Swantje Mü ; ller¹ ; Wolfgang Bildl¹ ; David Baehrens¹ ; Bj&#246 ; rn Hü ; ber¹ ; Akos Kulik¹ ; ⁴ ; Nikolaj Kl&#246 ; cker³ ; Uwe Schulte¹ ; ² ; ⁴ ; ^{uwe.schulte@physiologie.uni-freiburg.de} ; Bernd Fakler¹ ; ⁴ ; ^{bernd.fakler@physiologie.uni-freiburg.de}
• 刊名：Neuron
• 出版年：2012
• 期刊代码：45_08966273
• 类别：neu
• 出版时间：24 May, 2012
• 卷：74
• 期：4
• 页码：621-633
• 文件大小：1511 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

AMPA-type glutamate receptors (AMPARs) are responsible for a variety of processes in the mammalian brain including fast excitatory neurotransmission, postsynaptic plasticity, or synapse development. Here, with comprehensive and quantitative proteomic analyses, we demonstrate that native AMPARs are macromolecular complexes with a large molecular diversity. This diversity results from coassembly of the known AMPAR subunits, pore-forming GluA and three types of auxiliary proteins, with 21 additional constituents, mostly secreted proteins or transmembrane proteins of different classes. Their integration at distinct abundance and stability establishes the heteromultimeric architecture of native AMPAR complexes: a defined core with a variable periphery resulting in an apparent molecular mass between 0.6 and 1 MDa. The additional constituents change the gating properties of AMPARs and provide links to the protein dynamics fundamental for the complex role of AMPARs in formation and operation of glutamatergic synapses.