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Interaction Proteomics Reveals Brain Region-Specific AMPA Receptor Complexes
Abstract
Fast excitatory synaptic transmission in the brain is mediated by glutamate acting on postsynaptic AMPA receptors. Recent studies have revealed a substantial number of AMPA receptor auxiliary proteins, which potentially contribute to the regulation of AMPA receptor trafficking, subcellular receptor localization, and receptor gating properties. Here we examined the AMPA receptor interactomes from cortex, hippocampus, and cerebellum by comprehensive interaction proteomics. The study reveals that AMPA receptor auxiliary proteins are engaged in distinct brain region-specific AMPA receptors subcomplexes, which might underlie brain region-specific differential regulation of AMPA receptor properties. Depending on the brain region, an interacting protein can be involved in an AMPA and a non-AMPA receptor complex.
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SynDIG4 associates with both GluA1-and GluA2-containing AMPARs.
“Although SynDIG4 associates with both GluA1-and GluA2-containing AMPARs (Shanks et al., 2012; Schwenk et al., 2012; Chen et al., 2014) and loss of SynDIG4 leads to decreased surface expression of GluA1 and GluA2 in brain lysates (Troyano-Rodriguez et al., 2019) and reduced density of extrasynaptic GluA1 and GluA2 in cultured neurons (Matt et al., 2018), there are some aspects of SynDIG4 function”
From Loss of SynDIG4/PRRT1 alters distribution of AMPA receptors in Rab4- and Rab11-positive endosomes and impairs basal AMPA receptor recycling (2025) · cites this paper as Chen et al., 2014
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Regulation of AMPA receptor trafficking and synaptic plasticity
Anggono, V., & Huganir, R. L. (2012) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2011.12.006 · Cited by 588
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Milestone Review: Unlocking the Proteomics of Glycine Receptor Complexes
Fraser, S. D., Klaassen, R. V., Villmann, C., Smit, A. B., & Harvey, R. J. (2025) · Journal of Neurochemistry · doi:10.1111/jnc.70061 · Cited by 10
“…the use of knockout tissue as a negative control; or (iii) Using gene-editing technologies to introduce epitopes (e.g., myc, pHluorin or Venus tags) into the gene/protein of interest (Schwenk et al. 2009, 2012; Heller et al. 2012; Chen et al. 2014; Nakamura et al. 2016; van der Spek et al. 2022).”
Self-citationHe, C.-W., & Díaz, E. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1568908 · Cited by 3
Metadata
- Authors
- Chen, N., Pandya, N. J., Koopmans, F., Castelo-Székelv, V., van der Schors, R. C., Smit, A. B., & Li, K. W.
- Affiliations
- Department of Molecular and Cellular Neurobiology, and ‡Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, VU University, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands
- Venue
- Journal of Proteome Research
- Publisher
- American Chemical Society (ACS)
- Published
- 2014-11-19
- Volume
- 13
- Issue
- 12
- Pages
- 5695-5706
- ISSN
- 1535-3893
- 1535-3907
- Cited by
- 62
- References
- 2
- Language
- en
- Funders
- European Commission (242167)
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek (645.000.003)
- Netherlands Institute for Systems Biology
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