The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
EphB-Mediated Degradation of the RhoA GEF Ephexin5 Relieves a Developmental Brake on Excitatory Synapse Formation
Open accessAbstract
The mechanisms that promote excitatory synapse formation and maturation have been extensively studied. However, the molecular events that limit excitatory synapse development so that synapses form at the right time and place and in the correct numbers are less well understood. We have identified a RhoA guanine nucleotide exchange factor, Ephexin5, which negatively regulates excitatory synapse development until EphrinB binding to the EphB receptor tyrosine kinase triggers Ephexin5 phosphorylation, ubiquitination, and degradation. The degradation of Ephexin5 promotes EphB-dependent excitatory synapse development and is mediated by Ube3A, a ubiquitin ligase that is mutated in the human cognitive disorder Angelman syndrome and duplicated in some forms of Autism Spectrum Disorders (ASDs). These findings suggest that aberrant EphB/Ephexin5 signaling during the development of synapses may contribute to the abnormal cognitive function that occurs in Angelman syndrome and, possibly, ASDs.
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“using array tomography (AT), a powerful tool for high resolution imaging and quantification of synaptic density in vivo (Greer et al., 2010; Margolis et al., 2010; Micheva and Smith, 2007; Ross et al., 2010).”
From Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner (2012) · cites this paper as Margolis et al., 2010
Experimental — accuracy not yet measured
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
Hershko, A., & Ciechanover, A. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.425 · Cited by 8,840
A simple method for organotypic cultures of nervous tissue
Stoppini, L., Buchs, P., & Muller, D. (1991) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(91)90128-m · Cited by 3,096
Germline Transmission and Tissue-Specific Expression of Transgenes Delivered by Lentiviral Vectors
Lois, C., Hong, E. J., Pease, S., Brown, E. J., & Baltimore, D. (2002) · Science · doi:10.1126/science.1067081 · Cited by 1,992
GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors
Rossman, K. L., Der, C. J., & Sondek, J. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1587 · Cited by 1,697
UBE3A/E6-AP mutations cause Angelman syndrome
Kishino, T., Lalande, M., & Wagstaff, J. E. (1997) · Nature Genetics · doi:10.1038/ng0197-70 · Cited by 1,304
Schaeren‐Wiemers, N., & Gerfin-Moser, A. (1993) · Histochemistry and Cell Biology · doi:10.1007/bf00267823 · Cited by 1,151
THE EPHRINS AND EPH RECEPTORS IN NEURAL DEVELOPMENT
Flanagan, J. G., & Vanderhaeghen, P. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.309 · Cited by 1,091
Evidence for a Role of Dendritic Filopodia in Synaptogenesis and Spine Formation
Ziv, N. E., & Smith, S. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80283-4 · Cited by 882
Jiang, Y.-H., Armstrong, D., Albrecht, U., Atkins, C. M., Noebels, J. L., Eichele, G., Sweatt, J. D., & Beaudet, A. L. (1998) · Neuron · doi:10.1016/s0896-6273(00)80596-6 · Cited by 852
Xia, Z., Dudek, H., Miranti, C. K., & Greenberg, M. E. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-17-05425.1996 · Cited by 787
Self-citationMicheva, K. D., & Smith, S. J. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.014 · Cited by 787
EphB Receptors Interact with NMDA Receptors and Regulate Excitatory Synapse Formation
Dalva, M. B., Takasu, M. A., Lin, M. Z., Shamah, S. M., Hu, L. S., Gale, N. W., & Greenberg, M. E. (2000) · Cell · doi:10.1016/s0092-8674(00)00197-5 · Cited by 727
Self-citationActivity-dependent regulation of inhibitory synapse development by Npas4
Lin, Y., Bloodgood, B. L., Hauser, J. L., Lapan, A. D., Koon, A. C., Kim, T.-K., Hu, L. S., Malik, A. N., & Greenberg, M. E. (2008) · Nature · doi:10.1038/nature07319 · Cited by 639
Self-citationCell adhesion molecules: signalling functions at the synapse
Dalva, M. B., McClelland, A. C., & Kayser, M. S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2075 · Cited by 620
Activity-Dependent Regulation of MEF2 Transcription Factors Suppresses Excitatory Synapse Number
Flavell, S. W., Cowan, C. W., Kim, T.-K., Greer, P. L., Lin, Y., Paradis, S., Griffith, E. C., Hu, L. S., Chen, C., & Greenberg, M. E. (2006) · Science · doi:10.1126/science.1122511 · Cited by 573
Self-citationShamah, S. M., Lin, M. Z., Goldberg, J. L., Estrach, S., Şahin, M., Hu, L. S., Bazalakova, M. H., Neve, R. L., Corfas, G., Debant, A., et al. (2001) · Cell · doi:10.1016/s0092-8674(01)00314-2 · Cited by 544
Self-citationControl of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling
Murai, K. K., Nguyen, L. N., Irie, F., Yamaguchi, Y., & Pasquale, E. B. (2003) · Nature Neuroscience · doi:10.1038/nn994 · Cited by 516
Penzes, P., Beeser, A., Chernoff, J., Schiller, M. R., Eipper, B. A., Mains, R. E., & Huganir, R. L. (2003) · Neuron · doi:10.1016/s0896-6273(02)01168-6 · Cited by 466
Bidirectional modulation of synaptic functions by Eph/ephrin signaling
Klein, R. (2008) · Nature Neuroscience · doi:10.1038/nn.2231 · Cited by 431
Tashiro, A. (2000) · Cerebral Cortex · doi:10.1093/cercor/10.10.927 · Cited by 416
Bidirectional Eph–ephrin signaling during axon guidance
Egea, J., & Klein, R. (2007) · Trends in Cell Biology · doi:10.1016/j.tcb.2007.03.004 · Cited by 403
Regulation of Dendritic Spine Morphology by SPAR, a PSD-95-Associated RapGAP
Pak, D. T. S., Yang, S., Rudolph-Correia, S., Kim, E., & Sheng, M. (2001) · Neuron · doi:10.1016/s0896-6273(01)00355-5 · Cited by 395
Aghazadeh, B., Lowry, W. E., Huang, X.-Y., & Rosen, M. K. (2000) · Cell · doi:10.1016/s0092-8674(00)00085-4 · Cited by 383
Tolias, 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
Self-citationUbe3a is required for experience-dependent maturation of the neocortex
Yashiro, K., Riday, T. T., Condon, K. H., Roberts, A. C., Bernardo, D. R., Prakash, R., Weinberg, R. J., Ehlers, M. D., & Philpot, B. D. (2009) · Nature Neuroscience · doi:10.1038/nn.2327 · Cited by 328
Kinase-Independent Requirement of EphB2 Receptors in Hippocampal Synaptic Plasticity
Kadow, I. C. G., Körte, M., Wolfer, D. P., Wilkinson, G. A., Unsicker, K., Lipp, H., Bonhoeffer, T., & Klein, R. (2001) · Neuron · doi:10.1016/s0896-6273(01)00550-5 · Cited by 311
Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism
Fu, W., Chen, Y., Şahin, M., Zhao, X.-S., Shi, L., Bikoff, J. B., Lai, K., Yung, W., Fu, A. K. Y., Greenberg, M. E., et al. (2006) · Nature Neuroscience · doi:10.1038/nn1811 · Cited by 311
Self-citationMultiple EphB receptor tyrosine kinases shape dendritic spines in the hippocampus
Henkemeyer, M. J., Itkis, O. S., Ngo, M., Hickmott, P. W., & Ethell, I. M. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200306033 · Cited by 311
EphB/syndecan-2 signaling in dendritic spine morphogenesis
Ethell, I. M., Irie, F., Kalo, M. S., Couchman, J. R., Pasquale, E. B., & Yamaguchi, Y. (2001) · Neuron · doi:10.1016/s0896-6273(01)00440-8 · Cited by 309
Hippocampal plasticity requires postsynaptic ephrinBs
Kadow, I. C. G., Körte, M., Adelmann, G., Plück, A., Kullander, K., Adams, R. H., Frotscher, M., Bonhoeffer, T., & Klein, R. (2003) · Nature Neuroscience · doi:10.1038/nn1164 · Cited by 255
Eph-Dependent Tyrosine Phosphorylation of Ephexin1 Modulates Growth Cone Collapse
Şahin, M., Greer, P. L., Lin, M. Z., Poucher, H. K., Eberhart, J. K., Schmidt, S., Wright, T. M., Shamah, S. M., O’Connell, S., Cowan, C. W., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.01.030 · Cited by 243
Self-citationParadis, S., Harrar, D. B., Lin, Y., Koon, A. C., Chatterjee, J. H., Griffith, E. C., Zhu, L., Brass, L. F., Chen, C., & Greenberg, M. E. (2007) · Neuron · doi:10.1016/j.neuron.2006.12.012 · Cited by 238
Self-citationIntracellular and Trans-Synaptic Regulation of Glutamatergic Synaptogenesis by EphB Receptors
Kayser, M. S., McClelland, A. C., Hughes, E. G., & Dalva, M. B. (2006) · Journal of Neuroscience · doi:10.1523/jneurosci.3072-06.2006 · Cited by 222
EphB Receptors Couple Dendritic Filopodia Motility to Synapse Formation
Kayser, M. S., Nolt, M. J., & Dalva, M. B. (2008) · Neuron · doi:10.1016/j.neuron.2008.05.007 · Cited by 212
Structural basis for the selective activation of Rho GTPases by Dbl exchange factors
Snyder, J. T., Worthylake, D. K., Rossman, K. L., Betts, L., Pruitt, W. M., Siderovski, D. P., Der, C. J., & Sondek, J. (2002) · Nature Structural Biology · doi:10.1038/nsb796 · Cited by 209
Jontes, J. D., Buchanan, J., & Smith, S. J. (2000) · Nature Neuroscience · doi:10.1038/72936 · Cited by 204
Synapse development and plasticity: roles of ephrin/Eph receptor signaling
Lai, K., & Ip, N. Y. (2009) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2009.04.009 · Cited by 197
Ephrin-B reverse signaling promotes structural and functional synaptic maturation in vivo
Lim, B. K., Matsuda, N., & Poo, M. (2008) · Nature Neuroscience · doi:10.1038/nn2033 · Cited by 117
EphA4-Mediated Rho Activation via Vsm-RhoGEF Expressed Specifically in Vascular Smooth Muscle Cells
Ogita, H., Kunimoto, S., Kamioka, Y., Sawa, H., Masuda, M., & Mochizuki, N. (2003) · Circulation Research · doi:10.1161/01.res.0000079310.81429.c8 · Cited by 113
Ephrin-A1 Induces c-Cbl Phosphorylation and EphA Receptor Down-Regulation in T Cells
Sharfe, N., Freywald, A., Toro-Montoya, A. I., & Roifman, C. M. (2003) · The Journal of Immunology · doi:10.4049/jimmunol.170.12.6024 · Cited by 64
Ligand Binding Induces Cbl‐Dependent EphB1 Receptor Degradation Through the Lysosomal Pathway
Fasen, K., Cerretti, D. P., & Huynh‐Do, U. (2007) · Traffic · doi:10.1111/j.1600-0854.2007.00679.x · Cited by 45
The Angelman Syndrome Protein Ube3A Regulates Synapse Development by Ubiquitinating Arc
Greer, P. L., Hanayama, R., Bloodgood, B. L., Mardinly, A. R., Lipton, D. M., Flavell, S. W., Kim, T.-K., Griffith, E. C., Waldon, Z., Maehr, R., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.026 · Cited by 30
Self-citation
Research works printed but not linked: 1
- Micheva, K.D., and Smith, S.J. (2007). Array tomography: a new tool for imaging the molecular architecture and ultrastructure of neural circuits. Neuron 55, 25–36. · DOI · Paper page
Cited by
Sorted by citations
Microglia Sculpt Postnatal Neural Circuits in an Activity and Complement-Dependent Manner
Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012) · Neuron · doi:10.1016/j.neuron.2012.03.026 · Cited by 4,089
Self-citationExcitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders
Nelson, S. B., & Valakh, V. (2015) · Neuron · doi:10.1016/j.neuron.2015.07.033 · Cited by 1,001
Regulating Rho GTPases and their regulators
Hodge, R. G., & Ridley, A. J. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.67 · Cited by 897
Mechanisms of ephrin–Eph signalling in development, physiology and disease
Kania, A., & Klein, R. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.16 · Cited by 645
Eph Receptor Signaling and EphrinsPreprint
Lisabeth, E. M., Falivelli, G., & Pasquale, E. B. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a009159 · Cited by 448
Metadata
- Authors
- Margolis, S. S., Salogiannis, J., Lipton, D. M., Mandel-Brehm, C., Wills, Z. P., Mardinly, A. R., Hu, L., Greer, P. L., Bikoff, J. B., Ho, H.-Y. H., Soskis, M. J., Sahin, M., & Greenberg, M. E.
- Affiliations
- Harvard University (US)
- Corresponding author
- Greenberg, Michael E.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 143
- Issue
- 3
- Pages
- 442-455
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2967209
- OpenAlex
- W2031746153
- Cited by
- 256
- References
- 42
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 12 · 2023: 20 · 2022: 10 · 2021: 14 · 2020: 16 · 2019: 12 · 2018: 13 · 2017: 16 · 2016: 21 · 2015: 20 · 2014: 17 · 2013: 19 · 2012: 27
- FWCI
- 8.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1020 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5r01ns045500-29)
- National Institute on Aging (5T32AG00222-15, T32AG000222)
- National Institute of Neurological Disorders and Stroke (R01-NS-045500, R01 5R01NS045500)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Axon Guidance and Neuronal Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- EphB receptors, protein degradation, ubiquitination, UBE3A, Angelman syndrome, autism spectrum disorder, synapse maturation, receptor tyrosine kinase signaling
- MeSH terms
- Animals, Child, Child Development Disorders, Pervasive, Embryo, Mammalian, Humans, Synapses, Angelman Syndrome, Dentate Gyrus, Rats, Long-Evans, rhoA GTP-Binding Protein, Receptors, Eph Family, Ubiquitin-Protein Ligases, Mice, Rats, Gene Knockout 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
