Disrupted-in-Schizophrenia 1 (DISC1) regulates spines of the glutamate synapse via Rac1
Open accessAbstract
Synaptic spines are dynamic structures that regulate neuronal responsiveness and plasticity. We examined the role of the schizophrenia risk factor DISC1 in the maintenance of spine morphology and function. We found that DISC1 anchored Kalirin-7 (Kal-7), regulating access of Kal-7 to Rac1 and controlling the duration and intensity of Rac1 activation in response to NMDA receptor activation in both cortical cultures and rat brain in vivo. These results explain why Rac1 and its activator (Kal-7) serve as important mediators of spine enlargement and why constitutive Rac1 activation decreases spine size. This mechanism likely underlies disturbances in glutamatergic neurotransmission that have been frequently reported in schizophrenia that can lead to alteration of dendritic spines with consequential major pathological changes in brain function. Furthermore, the concept of a signalosome involving disease-associated factors, such as DISC1 and glutamate, may well contribute to the multifactorial and polygenetic characteristics of schizophrenia.
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
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?
Alterations in the regulation of actin at dendritic spines by neurodevelopmental disease-associated proteins such as DISC1, DTNBP1, SHANK3, PAK3, Oligophrenin and SRGAP2 produce deficits in synaptic plasticity and in the formation and consolidation of long-term memories.
“Moreover, alterations in the regulation of actin at dendritic spines, by neurodevelopmental disease-associated proteins such as DISC1, DTNBP1, SHANK3, PAK3, Oligophrenin and SRGAP2, have been shown to produce deficits in both synaptic plasticity and the formation and consolidation of long-term memories.23, 24, 25, 26, 27, 28, 29”
From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [24]
The Results section (“Long-term effects of DISC1 on dendritic spines”; page unavailable) reports that prolonged DISC1 knockdown reduced spine size, surface GluR1 expression and miniature excitatory postsynaptic current frequency. This supports a role for DISC1 in spine structure and synaptic function, but the paper does not show deficits in the formation or consolidation of long-term memories. Its findings do not establish the sentence’s broader claim for the other listed proteins. (LLM, conf=0.87)
Experimental — accuracy not yet measuredLoss of DISC1 leads to constituent activation of Rac1 signaling and spine loss via p21-activated kinase (PAK) signaling.
“Loss of DISC1 leads to constituent activation of Rac1 signaling and spine loss via p21-activated kinase (PAK) signaling131,132 (Fig. 4, orange).”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [131]
The Results (page not provided) report that DISC1 knockdown increased Rac1 activity and Pak1 phosphorylation, while prolonged knockdown markedly reduced spine size. The Methods (page not provided) describe Pak1 phosphorylation as an indicator of Rac1 activity; the paper does not establish that PAK signaling mediates the spine reduction. It reports spine shrinkage, rather than loss of spines. (LLM, conf=0.86)
Experimental — accuracy not yet measuredCYFIP1 is part of a growing number of mental illness-associated actin-regulatory molecules, including DISC1, DTNBP1, SHANK3, SRGAP2, Oligophrenin and the Abi1-WAVE2 complex, that act in Rac1-dependent pathways to regulate dendritic development and spine dynamics.
“Our results suggest that CYFIP1 is part of a growing number of mental illness-associated actin-regulatory molecules, including DISC1, DTNBP1, SHANK3, SRGAP2, Oligophrenin and the Abi1-WAVE2 complex that act in Rac1-dependent pathways to regulate dendritic development and spine dynamics.24, 25, 26, 27, 28, 29”
From The autism and schizophrenia associated gene CYFIP1 is critical for the maintenance of dendritic complexity and the stabilization of mature spines (2014) · cites this paper as [24]
DISC1 regulates the integrity of PFC spines by anchoring kalirin-7 (Kal7) and preventing its stimulation of Rac1 signaling.
“DISC1 also regulates the integrity of PFC spines by anchoring kalirin-7 (Kal7, the rodent homolog of Duo) and preventing its stimulation of Rac1 signaling131.”
From Stress weakens prefrontal networks: molecular insults to higher cognition (2015) · cites this paper as [131]
ErbB4 and DISC1 interact with PSD-95 in spines.
“ErbB4 and DISC1 interact with PSD-95 in spines54,58.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [54]
DISC1 interacts with several regulators of spine morphogenesis, most prominently the RacGEF kalirin-7.
“DISC1 is known to interact with several well-established regulators of spine morphogenesis, most prominently the RacGEF kalirin-7 (ref. 54).”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [54]
Long-term DISC1 knockdown in cortical neurons reduces spine area.
“Long-term DISC1 knockdown in cortical neurons reduces spine area54.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [54]
Kalirin-7, through activation of its downstream effector Rac1, directly regulates the effects of DISC1 on spine morphology.
“Recently, kalirin-7, via activation of its downstream effector Rac1, was found to directly regulate the effects of DISC1 on spine morphology54.”
From Dendritic spine pathology in neuropsychiatric disorders (2011) · cites this paper as [54]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Structural basis of long-term potentiation in single dendritic spines
Matsuzaki, M., Honkura, N., Ellis-Davies, G. C. R., & Kasai, H. (2004) · Nature · doi:10.1038/nature02617 · Cited by 2,500 · see citing works
Decreased Dendritic Spine Density on Prefrontal Cortical Pyramidal Neurons in Schizophrenia
Glantz, L. A., & Lewis, D. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.1.65 · Cited by 1,636 · see citing works
Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation
Shi, S.-H., Hayashi, Y., Petralia, R. S., Zaman, S. H., Wenthold, R. J., Svoboda, K., & Malinow, R. (1999) · Science · doi:10.1126/science.284.5421.1811 · Cited by 1,276 · see citing works
Rapid Dendritic Morphogenesis in CA1 Hippocampal Dendrites Induced by Synaptic Activity
Maletić‐Savatić, M., Malinow, R., & Svoboda, K. (1999) · Science · doi:10.1126/science.283.5409.1923 · Cited by 1,189 · see citing works
Transient and persistent dendritic spines in the neocortex in vivo
Holtmaat, A. J. G. D., Trachtenberg, J. T., Wilbrecht, L., Shepherd, G. M., Zhang, X., Knott, G. W., & Svoboda, K. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.003 · Cited by 1,131 · see citing works
The Postsynaptic Architecture of Excitatory Synapses: A More Quantitative View
Sheng, M., & Hoogenraad, C. C. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060805.160029 · Cited by 1,010 · see citing works
The Emerging Role of Glutamate in the Pathophysiology and Treatment of Schizophrenia
GOFF, D. C., & Coyle, J. T. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.9.1367 · Cited by 914 · see citing works
Rapid Actin-Based Plasticity in Dendritic Spines
Fischer, M., Kaech, S., Knutti, D., & Matus, A. (1998) · Neuron · doi:10.1016/s0896-6273(00)80467-5 · Cited by 905 · see citing works
Association within a family of a balanced autosomal translocation with major mental illness
St Clair, D., Blackwood, D., Muir, W., Walker, M., St Clair, D., Muir, W., Carothers, A., Spowart, G., Gosden, C., & Evans, H. J. (1990) · The Lancet · doi:10.1016/0140-6736(90)91520-k · Cited by 727 · see citing works
Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia
Garey, L. J., Ong, W., Patel, T. S., Kanani, M., Davis, A., Mortimer, A. M., Barnes, T., & Hirsch, S. R. (1998) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.65.4.446 · Cited by 719 · see citing works
Schizophrenia as a Disorder of Developmentally Reduced Synaptic Connectivity
McGlashan, T. H. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.7.637 · Cited by 655 · see citing works
DISC1 and PDE4B Are Interacting Genetic Factors in Schizophrenia That Regulate cAMP Signaling
Millar, J. K., Pickard, B. S., Mackie, S., James, R., Christie, S., Buchanan, S. R., Malloy, M. P., Chubb, J. E., Huston, E., Baillie, G. S., et al. (2005) · Science · doi:10.1126/science.1112915 · Cited by 648 · see citing works
Self-citationThe DISC locus in psychiatric illness
Chubb, J. E., Bradshaw, N. J., Soares, D. C., Porteous, D. J., & Millar, J. K. (2008) · Molecular Psychiatry · doi:10.1038/sj.mp.4002106 · Cited by 542 · see citing works
A schizophrenia-associated mutation of DISC1 perturbs cerebral cortex development
Kamiya, A., Kubo, K., Tomoda, T., Takaki, M., Youn, R., Ozeki, Y., Sawamura, N., Park, U., Kudo, C., Okawa, M., et al. (2005) · Nature Cell Biology · doi:10.1038/ncb1328 · Cited by 531 · see citing works
Self-citationVariation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia
Callicott, J. H., Straub, R. E., Pezawas, L., Egan, M. F., Mattay, V. S., Hariri, A. R., Verchinski, B. A., Meyer‐Lindenberg, A., Balkissoon, R., Kolachana, B. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500515102 · Cited by 512 · see citing works
Disruption of GW bodies impairs mammalian RNA interference
Jakymiw, A., Lian, S., Eystathioy, T., Li, S., Satoh, M., Hamel, J. C., Fritzler, M. J., & Chan, E. K. L. (2005) · Nature Cell Biology · doi:10.1038/ncb1334 · Cited by 496 · see citing works
Differential effects of the Rac GTPase on Purkinje cell axons and dendritic trunks and spines
Luo, L., Hensch, T. K., Ackerman, L. D., Barbel, S., Jan, L. Y., & Jan, Y. N. (1996) · Nature · doi:10.1038/379837a0 · Cited by 453 · see citing works
Steward, O., & Worley, P. F. (2001) · Neuron · doi:10.1016/s0896-6273(01)00275-6 · Cited by 450 · see citing works
Early Detection and Intervention With Schizophrenia: Rationale
McGlashan, T. H., & Johannessen, J. O. (1996) · Schizophrenia Bulletin · doi:10.1093/schbul/22.2.201 · Cited by 416 · see citing works
Tashiro, A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.927 · Cited by 416 · see citing works
Camargo, L. M., Collura, V, Rain, J.-C., Mizuguchi, K., Hermjakob, H., Kerrien, S., Bonnert, T. P., Whiting, P. J., & Brandon, N. J. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4001880 · Cited by 405 · see citing works
Self-citationBringing Order to the Glutamate Chaos in Schizophrenia
Moghaddam, B. (2003) · Neuron · doi:10.1016/s0896-6273(03)00757-8 · Cited by 403 · see citing works
Mirnics, K., Middleton, F. A., Lewis, D. A., & Levitt, P. R. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01862-2 · Cited by 393 · 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
Self-citationTolias, K. F., Bikoff, J. B., Burette, A., Paradis, S., Harrar, D., Tavazoie, S., Weinberg, R. J., & Greenberg, M. E. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.024 · Cited by 365 · see citing works
Spine architecture and synaptic plasticity
Carlisle, H. J., & Kennedy, M. B. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.01.008 · Cited by 351 · see citing works
Cannon, T. D., Hennah, W., van Erp, T. G. M., Thompson, P. M., Lonnqvist, J., Huttunen, M., Gasperoni, T., Tuulio-Henriksson, A., Pirkola, T., Toga, A. W., et al. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.11.1205 · Cited by 337 · see citing works
Jaaro-Peled, H., Hayashi‐Takagi, A., Seshadri, S., Kamiya, A., Brandon, N. J., & Sawa, A. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.05.007 · Cited by 315 · see citing works
Self-citationThe spectrin repeat: a structural platform for cytoskeletal protein assemblies
Djinović‐Carugo, K., Gautel, M., Ylänne, J., & Young, P. W. (2002) · FEBS Letters · doi:10.1016/s0014-5793(01)03304-x · Cited by 289 · see citing works
First in vivo evidence of an NMDA receptor deficit in medication-free schizophrenic patients
Pilowsky, L. S., Bressan, R. A., Stone, J. M., Erlandsson, K., Mulligan, R. S., Krystal, J. H., & Ell, P. J. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001751 · Cited by 278 · see citing works
Disc1 is mutated in the 129S6/SvEv strain and modulates working memory in mice
Koike, H., Arguello, P. A., Kvajo, M., Karayiorgou, M., & Gogos, J. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0511189103 · Cited by 276 · see citing works
Kvajo, M., McKellar, H., Arguello, P. A., Drew, L. J., Moore, H., MacDermott, A. B., Karayiorgou, M., & Gogos, J. A. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0802615105 · Cited by 268 · see citing works
Steen, R. G., Hamer, R. M., & Lieberman, J. A. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300850 · Cited by 254 · see citing works
Hill, J. J., Hashimoto, T., & Lewis, D. A. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001792 · Cited by 228 · see citing works
Saneyoshi, T., Wayman, G. A., Fortin, D. A., Davare, M. A., Hoshi, N., Nozaki, N., Natsume, T., & Soderling, T. R. (2008) · Neuron · doi:10.1016/j.neuron.2007.11.016 · Cited by 228 · see citing works
DISC1 Regulates the Transport of the NUDEL/LIS1/14-3-3ε Complex through Kinesin-1
Taya, S., Shinoda, T., Tsuboi, D., Uraguchi‐Asaki, J., Nagai, K., Hikita, T., Kuroda, S., Kuroda, K., Shimizu, M., Hirotsune, S., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.3826-06.2006 · Cited by 222 · see citing works
Disulfide-Linked Head-to-Head Multimerization in the Mechanism of Ion Channel Clustering by PSD-95
Hsueh, Y., Kim, E., & Sheng, M. (1997) · Neuron · doi:10.1016/s0896-6273(00)80319-0 · Cited by 205 · see citing works
A Review of Disrupted-in-Schizophrenia-1 (disc1): Neurodevelopment, Cognition, and Mental Conditions
Ishizuka, K., Paek, M., Kamiya, A., & Sawa, A. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.065 · Cited by 190 · see citing works
Self-citationKalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes
Cahill, M. E., Xie, Z., Day, M., Photowala, H., Barbolina, M. V., Miller, C. A., Weiss, C., Radulovic, J., Sweatt, J. D., Disterhoft, J. F., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904636106 · Cited by 170 · see citing works
Self-citationSchurov, I., Handford, E. J., Brandon, N. J., & Whiting, P. J. (2004) · Molecular Psychiatry · doi:10.1038/sj.mp.4001574 · Cited by 163 · see citing works
Self-citationMurdoch, H., Mackie, S., Collins, D. M., Hill, E. V., Bolger, G. B., Klußmann, E., Porteous, D. J., Millar, J. K., & Houslay, M. D. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1493-07.2007 · Cited by 152 · see citing works
Self-citationBolger, G. B., Baillie, G. S., Li, X., et al. (2006) · Biochemical Journal · doi:10.1042/bj20060423 · Cited by 147 · see citing works
Structural plasticity with preserved topology in the postsynaptic protein network
Blanpied, T. A., Kerr, J. M., & Ehlers, M. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0711669105 · Cited by 133 · see citing works
Cai, X., Gu, Z., Zhong, P., Ren, Y., & Yan, Z. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m203752200 · Cited by 130 · see citing works
Self-citationDISC1 immunoreactivity at the light and ultrastructural level in the human neocortex
Kirkpatrick, B., Xu, L., Cascella, N., Ozeki, Y., Sawa, A., & Roberts, R. C. (2006) · Journal of Comparative Neurology · doi:10.1002/cne.21007 · Cited by 104 · see citing works
Self-citationMa, X., Wang, Y., Ferraro, F., Mains, R. E., & Eipper, B. A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5283-07.2008 · Cited by 97 · see citing works
Schizophrenia as a Disorder of Neuroplasticity
McCullumsmith, R. E., Clinton, S. M., & Meador‐Woodruff, J. H. (2004) · International review of neurobiology · doi:10.1016/s0074-7742(04)59002-5 · Cited by 73 · see citing works
Rabiner, C. A., Mains, R. E., & Eipper, B. A. (2005) · The Neuroscientist · doi:10.1177/1073858404271250 · Cited by 66 · see citing works
Evidence that many of the DISC1 isoforms in C57BL/6J mice are also expressed in 129S6/SvEv mice
Ishizuka, K., Chen, J., Taya, S., Li, W., Millar, J. K., Xu, Y., Clapcote, S. J., Hookway, C., Morita, M., Kamiya, A., et al. (2007) · Molecular Psychiatry · doi:10.1038/sj.mp.4002024 · Cited by 47 · see citing works
Self-citationHarrison, P. J., & West, V. A. (2006) · Molecular Psychiatry · doi:10.1038/sj.mp.4001886 · Cited by 33 · see citing works
Hashimoto, R., Tankou, S. K., Takeda, M., et al. (2007) · Drugs of today · doi:10.1358/dot.2007.43.9.1088821 · Cited by 27 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Dendritic spine pathology in neuropsychiatric disorders
Penzes, P., Cahill, M. E., Jones, K. A., VanLeeuwen, J.-E., & Woolfrey, K. M. (2011) · Nature Neuroscience · doi:10.1038/nn.2741 · Cited by 1,523 · see citing works
Self-citationStress weakens prefrontal networks: molecular insults to higher cognition
Arnsten, A. F. T. (2015) · Nature Neuroscience · doi:10.1038/nn.4087 · Cited by 752 · see citing works
Dendritic spine pathology in schizophrenia
Glausier, J. R., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2012.04.044 · Cited by 581 · see citing works
Gao, R., & Penzes, P. (2015) · Current Molecular Medicine · doi:10.2174/1566524015666150303003028 · Cited by 516 · see citing works
“Indeed, long-term DISC1 knockdown leads to reduced spine area in cortical neurons [103].”
BackgroundSelf-citationStructural plasticity upon learning: regulation and functions
Caroni, P., Donato, F., & Muller, D. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3258 · Cited by 491 · see citing works
Barry, G., Briggs, J. A., Vanichkina, D. P., Poth, E. M., Beveridge, N. J., Ratnu, V. S., Nayler, S. P., Nones, K., Hu, J., Bredy, T. W., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2013.45 · Cited by 394 · see citing works
Structural and synaptic plasticity in stress-related disorders
Christoffel, D. J., Golden, S. A., & Russo, S. J. (2011) · Reviews in the Neurosciences · doi:10.1515/rns.2011.044 · Cited by 334 · see citing works
Epigenetic regulation of RAC1 induces synaptic remodeling in stress disorders and depression
Golden, S. A., Christoffel, D. J., Heshmati, M., Hodes, G. E., Magida, J., Davis, K., Cahill, M. E., Dias, C., Ribeiro, E., Ables, J. L., et al. (2013) · Nature Medicine · doi:10.1038/nm.3090 · Cited by 322 · see citing works
Wang, J., Hodes, G. E., Zhang, H., Zhang, S., Zhao, W., Golden, S. A., Bi, W., Menard, C., Kana, V., Leboeuf, M., et al. (2018) · Nature Communications · doi:10.1038/s41467-017-02794-5 · Cited by 274 · see citing works
Deep molecular diversity of mammalian synapses: why it matters and how to measure it
O'Rourke, N. A., Weiler, N. C., Micheva, K. D., & Smith, S. J. (2012) · Nature Reviews Neuroscience · doi:10.1038/nrn3170 · Cited by 210 · see citing works
Microdeletions of 3q29 confer high risk for schizophrenia
Mulle, J. G., Dodd, A. F., McGrath, J. A., Wolyniec, P. S., Mitchell, A. A., Shetty, A. C., Sobreira, N. L., Valle, D., Rudd, M. K., Satten, G., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.07.013 · Cited by 223 · see citing works
Gandal, M. J., Sisti, J., Klook, K., Ortinski, P. I., Leitman, V, Liang, Y., Thieu, T., Anderson, R., Pierce, R. C., Jonak, G., et al. (2012) · Translational Psychiatry · doi:10.1038/tp.2012.69 · Cited by 204 · see citing works
Pathania, M., Davenport, E. C., Muir, J., Sheehan, D. F., López-Doménech, G., & Kittler, J. T. (2014) · Translational Psychiatry · doi:10.1038/tp.2014.16 · Cited by 189 · see citing works
Wnts in adult brain: from synaptic plasticity to cognitive deficiencies
Oliva, C. A., Vargas, J. Y., & Inestrosa, N. C. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00224 · Cited by 162 · see citing works
Myelin, myelin-related disorders, and psychosis
Mighdoll, M. I., Tao, R., Kleinman, J. E., & Hyde, T. M. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2014.09.040 · Cited by 135 · see citing works
DISC1: Structure, Function, and Therapeutic Potential for Major Mental Illness
Soares, D. C., Carlyle, B. C., Bradshaw, N. J., & Porteous, D. J. (2011) · ACS Chemical Neuroscience · doi:10.1021/cn200062k · Cited by 129 · see citing works
Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine
Kim, I. H., Rossi, M. A., Aryal, D. K., Racz, B., Kim, N., Uezu, A., Wang, F., Wetsel, W. C., Weinberg, R. J., Yin, H., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4015 · Cited by 127 · see citing works
Drug targets for cognitive enhancement in neuropsychiatric disorders.
Wallace, T. L., Ballard, T. M., Pouzet, B., Riedel, W. J., & Wettstein, J. G. (2011) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2011.03.022 · Cited by 127 · see citing works
Developmental vulnerability of synapses and circuits associated with neuropsychiatric disorders
Penzes, P., Buonanno, A., Passafaro, M., Sala, C., & Sweet, R. A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12261 · Cited by 125 · see citing works
Self-citationSynaptic Actin Dysregulation, a Convergent Mechanism of Mental Disorders?
Yan, Z., Kim, E., Datta, D., Lewis, D. A., & Soderling, S. H. (2016) · The Journal of Neuroscience · doi:10.1523/jneurosci.2360-16.2016 · Cited by 120 · see citing works
Self-citationShank3 Deficiency Induces NMDA Receptor Hypofunction via an Actin-Dependent Mechanism
Duffney, L. J., Wei, J., Cheng, J., Liu, W., Smith, K. R., Kittler, J. T., & Yan, Z. (2013) · The Journal of Neuroscience · doi:10.1523/jneurosci.1175-13.2013 · Cited by 115 · see citing works
Self-citationPICK1 loss of function occludes homeostatic synaptic scaling
Anggono, V., Clem, R. L., & Huganir, R. L. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5633-10.2011 · Cited by 111 · see citing works
Carlson, G. C., Talbot, K., Halene, T. B., Gandal, M. J., Kazi, H. A., Schlosser, L., Phung, Q. H., Gur, R. E., Arnold, S. E., & Siegel, S. J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109625108 · Cited by 103 · see citing works
Kushima, I., Nakamura, Y., Aleksic, B., Ikeda, M., Ito, Y., Shiino, T., Okochi, T., Fukuo, Y., Ujike, H., Suzuki, M., et al. (2012) · Schizophrenia Bulletin · doi:10.1093/schbul/sbq118 · Cited by 92 · see citing works
Lanoue, V, Usardi, A., Sigoillot, S. M., Talleur, M., Iyer, K., Mariani, J., Isope, P., Vodjdani, G., Heintz, N., & Selimi, F. (2013) · Molecular Psychiatry · doi:10.1038/mp.2013.46 · Cited by 90 · see citing works
Carlisle, H. J., Luong, T. N., Medina-Marino, A., Schenker, L., Khorosheva, E., Indersmitten, T., Gunapala, K. M., Steele, A. D., O'Dell, T. J., Patterson, P. H., et al. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.5877-10.2011 · Cited by 74 · see citing works
Chen, S.-Y., Huang, P.-H., & Cheng, H.-J. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1018128108 · Cited by 73 · see citing works
Glutathione is a physiologic reservoir of neuronal glutamate
Koga, M., Serritella, A. V., Messmer, M. M., Hayashi-Takagi, A., Hester, L. D., Snyder, S. H., Sawa, A., & Sedlak, T. W. (2011) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2011.04.087 · Cited by 73 · see citing works
Self-citationDendritic spine actin cytoskeleton in autism spectrum disorder
Joensuu, M., Lanoue, V., & Hotulainen, P. (2018) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2017.08.023 · Cited by 65 · see citing works
Arnsten, A. F. T., & Wang, M. (2016) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103617 · Cited by 50 · see citing works
Rho GTPases in neurodegeneration diseases
DeGeer, J., & Lamarche-Vane, N. (2013) · Experimental Cell Research · doi:10.1016/j.yexcr.2013.06.016 · Cited by 46 · see citing works
Wang, Y., Sakano, H., Beebe, K., Brown, M. R., de Laat, R., Bothwell, M., Kulesza, R. J., & Rubel, E. W. (2014) · Journal of Comparative Neurology · doi:10.1002/cne.23520 · Cited by 40 · see citing works
Morris, D. W., Pearson, R. D., Cormican, P., Kenny, E. M., O'Dushlaine, C. T., Perreault, L.-P. L., Giannoulatou, E., Tropea, D., Maher, B. S., Wormley, B., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu025 · Cited by 42 · see citing works
Role of disrupted in schizophrenia 1 (DISC1) in stress-induced prefrontal cognitive dysfunction
Gamo, N. J., Duque, A., Paspalas, C. D., Kata, A., Fine, R., Boven, L., Bryan, C., Lo, T., Anighoro, K., Bermudez, L., et al. (2013) · Translational Psychiatry · doi:10.1038/tp.2013.104 · Cited by 37 · see citing works
Freire-Cobo, C., & Wang, J. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173362 · Cited by 11 · see citing works
- Authors
- Hayashi-Takagi, A., Takaki, M., Graziane, N., Seshadri, S., Murdoch, H., Dunlop, A. J., Makino, Y., Seshadri, A. J., Ishizuka, K., Srivastava, D. P., Xie, Z., Baraban, J. M., Houslay, M. D., Tomoda, T., Brandon, N. J., Kamiya, A., Yan, Z., Penzes, P., & Sawa, A.
- Affiliations
- Johns Hopkins University (US)
- University of Glasgow (GB)
- Northwestern University (US)
- Beckman Research Institute (US)
- Pfizer (United States) (US)
- University at Buffalo, State University of New York (US)
- Corresponding author
- Sawa, Akira
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2010-02-07
- Volume
- 13
- Issue
- 3
- Pages
- 327-332
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC2846623
- OpenAlex
- W2119383776
- Cited by
- 399
- References
- 51
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 14 · 2023: 9 · 2022: 17 · 2021: 12 · 2020: 24 · 2019: 20 · 2018: 26 · 2017: 22 · 2016: 33 · 2015: 36 · 2014: 25 · 2013: 32 · 2012: 38
- FWCI
- 18.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Research Portal (King's College London) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22791125)
- National Institute of Mental Health (MH 071316, MH-084233, MH084018, RC1MH088753, R01MH084233, MH‑088753, P20MH084018, R01MH069853, R56MH071316, R01MH071316, MH069853)
- National Institute of Neurological Disorders and Stroke (NS-048911, R01NS048911)
- National Center for Research Resources (P41RR001192)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- DISC1, schizophrenia, dendritic spines, Rac1, Kalirin-7, Rho GTPase signaling, NMDA receptor, glutamatergic synapses, synaptic plasticity, signalosome, glutamatergic neurotransmission, cortical neurons
- MeSH terms
- Animals, Cells, Cultured, Cerebral Cortex, Nerve Tissue Proteins, Neurons, Synapses, Time Factors, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Rats, Sprague-Dawley, Receptors, AMPA, Glutamic Acid, Excitatory Postsynaptic Potentials, Guanine Nucleotide Exchange Factors, rac1 GTP-Binding Protein, RNA Interference, Tissue Culture Techniques, Dendritic Spines, Rats, Gene Knockdown 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
