The DOI matches its Crossref record; 2 of the 2 references it cites were found in a registry or an index.
Mutually Dependent Clustering of SynDIG4/PRRT1 and AMPA Receptor Subunits GluA1 and GluA2 in Heterologous Cells and Primary Neurons
Abstract
Regulation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) at synapses is a predominant mechanism for regulating synaptic strength. We identified the transmembrane protein synapse differentiation-induced gene 1 (SynDIG1; SD1) as an AMPAR interacting protein that regulates excitatory synaptic strength and AMPAR number both in vitro and in vivo. The related protein SynDIG4 (SD4; also known as PRRT1) was identified in several independent proteomic screens in complex with AMPARs, suggesting that it may function as an AMPAR auxiliary factor. Here, we show that the co-expression of SD4 with GluA1 or GluA2 homomeric AMPARs in COS cells leads to a 50 or 33% increase in the mean area of AMPAR puncta, respectively. This effect is accentuated when AMPAR puncta are stratified for co-localization with SD4, resulting in a 100 and 65% increase in GluA1 and GluA2 puncta, respectively. Chimeric proteins expressing only the membrane bound domain of SD4 co-expressed with full-length GluA1 or GluA2 recapitulated the effects of wild-type (WT) SD4. Additionally, the mean puncta area of GluA1 or GluA2 chimeras expressing the membrane and C-terminal domains increased significantly when co-localized with WT SD4. Similarly, the co-expression of GluA1 or GluA2 with SD4 results in a significant increase in the mean area of SD4 puncta co-localized with GluA1 or GluA2, respectively. Last, we observed a significant increase in the co-localization of SD4 with GluA1 after glycine induced long-term potentiation (LTP). The mean size of GluA1 puncta was significantly increased when stratified, indicating that co-localization with SD4 increases synaptic GluA1 cluster size during LTP. These data indicate mutually dependent clustering of SD4 and AMPAR subunits both in COS cells and primary hippocampal neurons, suggesting a mechanism for increased synaptic strength during chemical LTP.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Endocytosis is likely required for the clustering of live-labeled GluA1 and GluA2, but not GluK2, with SynDIG4.
“Interestingly, our prior study investigating the distribution of SynDIG4 and AMPARs in heterologous cells proposed that endocytosis is likely required for the clustering of live-labeled GluA1 and GluA2, but not GluK2, with SynDIG4 (Plambeck et al., 2022).”
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 Plambeck et al., 2022
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms
Chen, L., Chetkovich, D. M., Petralia, R. S., Sweeney, N. T., Kawasaki, Y., Wenthold, R. J., Bredt, D. S., & Nicoll, R. A. (2000) · Nature · doi:10.1038/35050030 · Cited by 1,111
Kadriu, B., Musazzi, L., Johnston, J. N., Kalynchuk, L. E., Caruncho, H. J., Popoli, M., & Zarate, C. A. (2021) · Drug Discovery Today · doi:10.1016/j.drudis.2021.07.027 · Cited by 62
Flagged first, then by citations
Research works printed but not linked: 34
- Babaei, 2021, NMDA and AMPA receptors dysregulation in Alzheimer’s disease., Eur. J. Pharmacol., 908, 10.1016/j.ejphar.2021.174310 · DOI
- Ben-Yaacov, 2017, Molecular mechanism of AMPA receptor modulation by TARP/stargazin., Neuron, 93, 1126.e4, 10.1016/j.neuron.2017.01.032 · DOI
- Díaz, 2010, Regulation of AMPA receptors by transmembrane accessory proteins., Eur. J. Neurosci., 32, 261, 10.1111/j.1460-9568.2010.07357.x · DOI
- Freund, 2008, Proline-rich sequence recognition domains (PRD): ligands, function and inhibition., Handb. Exp. Pharmacol., 186, 407, 10.1007/978-3-540-72843-6_17 · DOI
- Ge, 2021, GluA1-homomeric AMPA receptor in synaptic plasticity and neurological diseases., Neuropharmacology, 197, 10.1016/j.neuropharm.2021.108708 · DOI
- Huganir, 2013, AMPARs and synaptic plasticity: the last 25 years., Neuron, 80, 704, 10.1016/j.neuron.2013.10.025 · DOI · Paper page
- Jackson, 2011, The expanding social network of ionotropic glutamate receptors: TARPs and other transmembrane auxiliary subunits., Neuron, 70, 178, 10.1016/j.neuron.2011.04.007 · DOI · Paper page
- Jacobi, 2017, Diversity in AMPA receptor complexes in the brain., Curr. Opin. Neurobiol., 45, 32, 10.1016/j.conb.2017.03.001 · DOI · Paper page
- Kalashnikova, 2010, SynDIG1: an activity-regulated, AMPA- receptor-interacting transmembrane protein that regulates excitatory synapse development., Neuron, 65, 80, 10.1016/j.neuron.2009.12.021 · DOI
- Kay, 2000, The importance of being proline: the interaction of proline-rich motifs in signaling proteins with their cognate domains., FASEB J. Off. Publ. Fed. Am. Soc. Exp. Biol., 14, 231, 10.1096/fasebj.14.2.231 · DOI
- Kirk, 2016, Distribution of the SynDIG4/proline-rich transmembrane protein 1 in rat brain., J. Comp. Neurol., 524, 2266, 10.1002/cne.23945 · DOI · Paper page
- Ling, 2016, Combined approaches of EPR and NMR illustrate only one transmembrane helix in the human IFITM3., Sci. Rep., 6, 10.1038/srep24029 · DOI
- Lissin, 1998, Activity differentially regulates the surface expression of synaptic AMPA and NMDA glutamate receptors., Proc. Natl. Acad. Sci. U.S.A., 95, 7097, 10.1073/pnas.95.12.7097 · DOI
- Lovero, 2013, SynDIG1 promotes excitatory synaptogenesis independent of AMPA receptor trafficking and biophysical regulation., PLoS One, 8, 10.1371/journal.pone.0066171 · DOI
- Lu, 2009, Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach., Neuron, 62, 254, 10.1016/j.neuron.2009.02.027 · DOI · Paper page
- Matt, 2018, SynDIG4/Prrt1 is required for excitatory synapse development and plasticity underlying cognitive function., Cell Rep., 22, 2246, 10.1016/j.celrep.2018.02.026 · DOI · Paper page
- Martin, 2021, Interaction and subcellular association of PRRT1/SynDIG4 with AMPA receptors., Front. Synaptic Neurosci., 13, 10.3389/fnsyn.2021.705664 · DOI · Paper page
- McAllister, 2007, Dynamic aspects of CNS synapse formation., Annu. Rev. Neurosci., 30, 425, 10.1146/annurev.neuro.29.051605.112830 · DOI · Paper page
- Plant, 2006, Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation., Nat. Neurosci., 9, 602, 10.1038/nn1678 · DOI · Paper page
- Sällman Almén, 2012, The dispanins: a novel gene family of ancient origin that contains 14 human members., PLoS One, 7, 10.1371/journal.pone.0031961 · DOI
- Sanderson, 2016, Receptor-dependent LTD requires transient synaptic incorporation of Ca2+-permeable AMPARs mediated by AKAP150-anchored PKA and calcineurin., Neuron, 89, 1000, 10.1016/j.neuron.2016.01.043 · DOI · Paper page
- Scheiffele, 2003, Cell-cell signaling during synapse formation in the CNS., Annu. Rev. Neurosci., 26, 485, 10.1146/annurev.neuro.26.043002.094940 · DOI
- Schwenk, 2012, High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes., Neuron, 74, 621, 10.1016/j.neuron.2012.03.034 · DOI · Paper page
- Schwenk, 2009, Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors., Science, 323, 1313, 10.1126/science.1167852 · DOI
- Shanks, 2012, Differences in AMPA and kainate receptor interactomes facilitate identification of AMPA receptor auxiliary subunit GSG1L., Cell Rep., 1, 590, 10.1016/j.celrep.2012.05.004 · DOI · Paper page
- Tomita, 2005, Stargazin modulates AMPA receptor gating and trafficking by distinct domains., Nature, 435, 1052, 10.1038/nature03624 · DOI · Paper page
- Tomita, 2003, Functional studies and distribution define a family of transmembrane AMPA receptor regulatory proteins., J. Cell Biol., 161, 805, 10.1083/jcb.200212116 · DOI
- Troyano-Rodriguez, 2019, PRRT1 regulates basal and plasticity-induced AMPA receptor trafficking., Mol. Cell. Neurosci., 98, 155, 10.1016/j.mcn.2019.06.008 · DOI · Paper page
- Twomey, 2016, Elucidation of AMPA receptor-stargazin complexes by cryo-electron microscopy., Science, 353, 83, 10.1126/science.aaf8411 · DOI
- von Engelhardt, 2010, CKAMP44: a brain-specific protein attenuating short-term synaptic plasticity in the dentate gyrus., Science, 327, 1518, 10.1126/science.1184178 · DOI
- Yount, 2010, Palmitoylome profiling reveals s-palmitoylation-dependent antiviral activity of IFITM3., Nat. Chem. Biol., 6, 610, 10.1038/nchembio.405 · DOI
- Yu, 2021, Hippocampal AMPA receptor assemblies and mechanism of allosteric inhibition., Nature, 594, 448, 10.1038/s41586-021-03540-0 · DOI
- Zhang, 2021, Gating and modulation of a hetero-octameric AMPA glutamate receptor., Nature, 594, 454, 10.1038/s41586-021-03613-0 · DOI
- Zhao, 2016, Architecture of fully occupied GluA2 AMPA receptor-TARP complex elucidated by Cryo-EM., Nature, 536, 108, 10.1038/nature18961 · DOI
Cited by
Sorted by citations
He, C.-W., & Díaz, E. (2025) · Frontiers in Pharmacology · doi:10.3389/fphar.2025.1568908 · Cited by 3
Self-citation
Metadata
- Authors
- Plambeck, K. E., He, C.-W., Navarro, H. H., & Díaz, E.
- Venue
- Frontiers in Molecular Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2022-04-08
- Volume
- 15
- ISSN
- 1662-5099
- PMC
- PMC9024365
- Cited by
- 7
- References
- 2
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review