Amino Acids

, Volume 44, Issue 5, pp 1247–1251 | Cite as

Interaction proteomics of the AMPA receptor: towards identification of receptor sub-complexes

Invited review

Abstract

AMPA receptors (AMPAR) are the main ligand-gated ion channels responsible for the fast excitatory synaptic transmission in the mammalian brain. Whereas a number of proteins that interact with AMPAR are known to be involved in the trafficking and localization of the receptor and/or the regulation of receptor channel properties, the protein composition of the AMPAR supra-complexes are largely unclear. Recent interaction proteomics report the presence of up to 34 proteins as high-confidence constituents of the AMPAR. It was proposed that the inner core of the receptor complex consists of the GluA tetramer and four auxiliary proteins comprising transmembrane AMPA receptor regulatory proteins and/or cornichons. The other AMPAR interactors, present in lower amount, may form the outer shell of the AMPAR with a range in size and variability.

Keywords

Synapse Excitatory neurotransmission AMPA receptor Protein complex Proteomics 

Abbreviations

AMPAR

AMPA receptor

BN-PAGE

Blue-native polyacrylamide gel electrophoresis

ESI

Electrospray

IP

Immuno-precipitation

MALDI

Matrix-assisted laser desorption ionization

MS

Mass spectrometry

TARP

Transmembrane AMPA receptor regulatory protein

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Anggono V, Huganir RL (2012) Regulation of AMPA receptor trafficking and synaptic plasticity. Curr Opin in Neurobiol 22:461–469CrossRefGoogle Scholar
  2. Granger AJ, Shi Y, Lu W, Cerpas M, Nicoll RA (2012) LTP requires a reserve pool of glutamate receptors independent of subunit type. Nature. doi: 10.1038/nature11775
  3. Jackson AC, Nicoll RA (2011) The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits. Neuron 70:178–199PubMedCrossRefGoogle Scholar
  4. Kalashnikova E, Lorca RA, Kaur I, Barisone GA, Li B, Ishimaru T, Trimmer JS, Mohapatra DP, Diaz E (2010) SynDIG1: an activity-regulated, AMPA-receptor-interacting transmembrane protein that regulates excitatory synapse development. Neuron 65:80–93PubMedCrossRefGoogle Scholar
  5. Li KW, Chen N, Klemmer P, Koopmans F, Karupothula R, Smit AB (2012) Identifying true protein complex constituents in interaction proteomics: the example of the DMXL2 protein complex. Proteomics 12:2428–2432PubMedCrossRefGoogle Scholar
  6. Lu W, Shi Y, Jackson AC, Bjorgan K, During MJ, Sprengel R, Seeburg PH, Nicoll RA (2009) Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 62:254–268PubMedCrossRefGoogle Scholar
  7. Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, Chisaka O, Jonas P, Schulte U, Fakler B, Klocker N (2009) Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors. Science 323:1313–1319PubMedCrossRefGoogle Scholar
  8. Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Muller CS, Bildl W, Baehrens D, Huber B, Kulik A, Klocker N, Schulte U, Fakler B (2012) High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes. Neuron 74:621–633PubMedCrossRefGoogle Scholar
  9. Shanks NF, Savas Jeffrey N, Maruo T, Cais O, Hirao A, Oe S, Ghosh A, Noda Y, Greger Ingo H, Yates John R, Nakagawa T (2012) Differences in AMPA and Kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L. Cell Rep 1:590–598PubMedCrossRefGoogle Scholar
  10. Shi Y, Lu W, Milstein AD, Nicoll RA (2009) The stoichiometry of AMPA receptors and TARPs varies by neuronal cell type. Neuron 62:633–640PubMedCrossRefGoogle Scholar
  11. Sierra AY, Gratacos E, Carrasco P, Clotet J, Urena J, Serra D, Asins G, Hegardt FG, Casals N (2008) CPT1c is localized in endoplasmic reticulum of neurons and has carnitine palmitoyltransferase activity. J Biol Chem 283:6878–6885PubMedCrossRefGoogle Scholar
  12. Straub C, Tomita S (2012) The regulation of glutamate receptor trafficking and function by TARPs and other transmembrane auxiliary subunits. Curr Opin Neurobiol 22:488–495PubMedCrossRefGoogle Scholar
  13. von Engelhardt J, Mack V, Sprengel R, Kavenstock N, Li KW, Stern-Bach Y, Smit AB, Seeburg PH, Monyer H (2010) CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus. Science 327:1518–1522CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Department of Molecular and Cellular Neurobiology, Faculty of Earth and Life Sciences, Center for Neurogenomics and Cognitive Research, Neuroscience Campus AmsterdamVU UniversityAmsterdamThe Netherlands

Personalised recommendations