Cited by 256Axon Guidance and Neuronal SignalingNeuroscience and Neuropharmacology ResearchGenetics and Neurodevelopmental Disorders

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EphB-Mediated Degradation of the RhoA GEF Ephexin5 Relieves a Developmental Brake on Excitatory Synapse Formation

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Margolis, Seth S., Salogiannis, John, Lipton, David M., Mandel-Brehm, Caleigh, Wills, Zachary P., Mardinly, Alan R., Hu, Linda, Greer, Paul L., Bikoff, Jay B., Ho, Hsin-Yi Henry, Soskis, Michael J., Sahin, Mustafa, Greenberg, Michael E.·2010·Cell

DOI 10.1016/j.cell.2010.09.038PMC PMC2967209

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Abstract

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.

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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: Margolis, Seth S.
Salogiannis, John
Wills, Zachary P.
Mardinly, Alan R.
Greer, Paul L.
Bikoff, Jay B.
Ho, Hsin-Yi Henry
Greenberg, Michael E.
Venue: Cell
Publisher: Elsevier BV
Published: 2010-10
Volume: 143
Issue: 3
Pages: 442-455
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2010.09.038
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

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EphB-Mediated Degradation of the RhoA GEF Ephexin5 Relieves a Developmental Brake on Excitatory Synapse Formation

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