Kalirin and Trio proteins serve critical roles in excitatory synaptic transmission and LTP
Open accessAbstract
The molecular mechanism underlying long-term potentiation (LTP) is critical for understanding learning and memory. CaMKII, a key kinase involved in LTP, is both necessary and sufficient for LTP induction. However, how CaMKII gives rise to LTP is currently unknown. Recent studies suggest that Rho GTPases are necessary for LTP. Rho GTPases are activated by Rho guanine exchange factors (RhoGEFs), but the RhoGEF(s) required for LTP also remain unknown. Here, using a combination of molecular, electrophysiological, and imaging techniques, we show that the RhoGEF Kalirin and its paralog Trio play critical and redundant roles in excitatory synapse structure and function. Furthermore, we show that CaMKII phosphorylation of Kalirin is sufficient to enhance synaptic AMPA receptor expression, and that preventing CaMKII signaling through Kalirin and Trio prevents LTP induction. Thus, our data identify Kalirin and Trio as the elusive targets of CaMKII phosphorylation responsible for AMPA receptor up-regulation during LTP.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
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?
Kalirin and Trio serve critical and functionally redundant roles in supporting excitatory synapse structure and function.
“Kalirin and Trio serve critical and functionally redundant roles in supporting excitatory synapse structure and function (32, 318).”
From Synaptic memory and CaMKII (2023) · cites this paper as [318]
Simultaneously inhibiting CaMKII signaling through Kalirin and Trio eliminates LTP.
“simultaneously inhibiting CaMKII signaling through Kalirin and Trio eliminates LTP (318).”
From Synaptic memory and CaMKII (2023) · cites this paper as [318]
Inhibiting Kalirin function alone has little effect on LTP.
“Although inhibiting Kalirin function alone has little effect on LTP (318, 319)”
From Synaptic memory and CaMKII (2023) · cites this paper as [318]
Cites
NMDA receptor-dependent long-term potentiation and long-term depression (LTP/LTD).
Luscher, C., & Malenka, R. C. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005710 · Cited by 1,110 · see citing works
Local, persistent activation of Rho GTPases during plasticity of single dendritic spines
Murakoshi, H., Wang, H., & Yasuda, R. (2011) · Nature · doi:10.1038/nature09823 · Cited by 564 · see citing works
Kalirin-7 Controls Activity-Dependent Structural and Functional Plasticity of Dendritic Spines
Xie, Z., Srivastava, D. P., Photowala, H., Kai, L., Cahill, M. E., Woolfrey, K. M., Shum, C. Y., Surmeier, D. J., & Penzes, P. (2007) · Neuron · doi:10.1016/j.neuron.2007.10.005 · Cited by 373 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
Dejanovic, B., Huntley, M. A., De Mazière, A., Meilandt, W. J., Wu, T., Srinivasan, K., Jiang, Z., Gandham, V., Friedman, B. A., Ngu, H., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.10.014 · Cited by 575 · see citing works
Dendritic structural plasticity and neuropsychiatric disease
Forrest, M. P., Parnell, E., & Penzes, P. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.16 · Cited by 464 · see citing works
Molecular Mechanisms of Early and Late LTP
Baltaci, S. B., Mogulkoc, R., & Baltaci, A. K. (2019) · Neurochemical Research · doi:10.1007/s11064-018-2695-4 · Cited by 152 · see citing works
Pinto, B., Morelli, G., Rastogi, M., Savardi, A., Fumagalli, A., Petretto, A., Bartolucci, M., Varea, E., Catelani, T., Contestabile, A., et al. (2020) · Neuron · doi:10.1016/j.neuron.2020.09.010 · Cited by 135 · see citing works
Nicoll, R. A., & Schulman, H. (2023) · Physiological Reviews · doi:10.1152/physrev.00034.2022 · Cited by 126 · see citing works
“Although inhibiting Kalirin function alone has little effect on LTP (318, 319), simultaneously inhibiting CaMKII signaling through Kalirin and Trio eliminates LTP (318).”
BackgroundSelf-citationReciprocal Activation within a Kinase-Effector Complex Underlying Persistence of Structural LTP
Saneyoshi, T., Matsuno, H., Suzuki, A., Murakoshi, H., Hedrick, N. G., Agnello, E., O’Connell, R., Stratton, M. M., Yasuda, R., & Hayashi, Y. (2019) · Neuron · doi:10.1016/j.neuron.2019.04.012 · Cited by 119 · see citing works
Barbosa, S., Greville-Heygate, S., Bonnet, M., Godwin, A., Fagotto-Kaufmann, C., Kajava, A. V., Laouteouet, D., Mawby, R., Wai, H. A., Dingemans, A. J. M., et al. (2020) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2020.01.018 · Cited by 104 · see citing works
- Authors
- Herring, B. E., & Nicoll, R. A.
- Affiliations
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2016-02-08
- Volume
- 113
- Issue
- 8
- Pages
- 2264-2269
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4776457
- OpenAlex
- W2272445359
- Cited by
- 98
- References
- 3
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 11 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 12 · 2019: 12 · 2018: 12 · 2017: 11 · 2016: 4
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- HHS | NIH | National Institute of Mental Health (MH038256, MH103398)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- Kalirin, trios, Rho GTPases, CaMKII, long-term potentiation, excitatory synaptic transmission, CaMKII phosphorylation, synaptic plasticity, learning and memory
- MeSH terms
- Animals, Humans, Models, Neurological, Nerve Tissue Proteins, Synaptic Transmission, Phosphoproteins, Phosphorylation, Up-Regulation, Receptors, N-Methyl-D-Aspartate, Protein Serine-Threonine Kinases, Long-Term Potentiation, Receptors, AMPA, Guanine Nucleotide Exchange Factors, Mice, Rats, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Gene Knockdown Techniques, Gene Knockout Techniques, CA1 Region, Hippocampal, HEK293 Cells, In Vitro Techniques
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
