دورية أكاديمية
EphA7 isoforms differentially regulate cortical dendrite development.
العنوان: | EphA7 isoforms differentially regulate cortical dendrite development. |
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المؤلفون: | Leonard CE; Department of Biology, Georgetown University, Washington, DC, United States of America.; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States of America., Baydyuk M; Department of Biology, Georgetown University, Washington, DC, United States of America., Stepler MA; Department of Biology, Georgetown University, Washington, DC, United States of America., Burton DA; Department of Biology, Georgetown University, Washington, DC, United States of America., Donoghue MJ; Department of Biology, Georgetown University, Washington, DC, United States of America.; Interdisciplinary Program in Neuroscience, Georgetown University, Washington, DC, United States of America. |
المصدر: | PloS one [PLoS One] 2020 Dec 04; Vol. 15 (12), pp. e0231561. Date of Electronic Publication: 2020 Dec 04 (Print Publication: 2020). |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: eCollection Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: San Francisco, CA : Public Library of Science |
مواضيع طبية MeSH: | Cerebral Cortex/*embryology , Dendrites/*metabolism , Receptor, EphA7/*metabolism, Animals ; Axons/metabolism ; Cells, Cultured ; Cerebral Cortex/metabolism ; Dendritic Spines/metabolism ; Male ; Mice, Inbred C57BL/embryology ; Neurons/metabolism ; Organogenesis ; Protein Isoforms/physiology ; Rats ; Rats, Sprague-Dawley/embryology ; Receptor, EphA7/physiology ; Signal Transduction |
مستخلص: | The shape of a neuron facilitates its functionality within neural circuits. Dendrites integrate incoming signals from axons, receiving excitatory input onto small protrusions called dendritic spines. Therefore, understanding dendritic growth and development is fundamental for discerning neural function. We previously demonstrated that EphA7 receptor signaling during cortical development impacts dendrites in two ways: EphA7 restricts dendritic growth early and promotes dendritic spine formation later. Here, the molecular basis for this shift in EphA7 function is defined. Expression analyses reveal that EphA7 full-length (EphA7-FL) and truncated (EphA7-T1; lacking kinase domain) isoforms are dynamically expressed in the developing cortex. Peak expression of EphA7-FL overlaps with dendritic elaboration around birth, while highest expression of EphA7-T1 coincides with dendritic spine formation in early postnatal life. Overexpression studies in cultured neurons demonstrate that EphA7-FL inhibits both dendritic growth and spine formation, while EphA7-T1 increases spine density. Furthermore, signaling downstream of EphA7 shifts during development, such that in vivo inhibition of mTOR by rapamycin in EphA7-mutant neurons ameliorates dendritic branching, but not dendritic spine phenotypes. Finally, direct interaction between EphA7-FL and EphA7-T1 is demonstrated in cultured cells, which results in reduction of EphA7-FL phosphorylation. In cortex, both isoforms are colocalized to synaptic fractions and both transcripts are expressed together within individual neurons, supporting a model where EphA7-T1 modulates EphA7-FL repulsive signaling during development. Thus, the divergent functions of EphA7 during cortical dendrite development are explained by the presence of two variants of the receptor. Competing Interests: The authors have declared that no competing interests exist. |
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المشرفين على المادة: | 0 (Protein Isoforms) EC 2.7.10.1 (Receptor, EphA7) |
تواريخ الأحداث: | Date Created: 20201204 Date Completed: 20210113 Latest Revision: 20240804 |
رمز التحديث: | 20240804 |
مُعرف محوري في PubMed: | PMC7717530 |
DOI: | 10.1371/journal.pone.0231561 |
PMID: | 33275600 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1932-6203 |
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DOI: | 10.1371/journal.pone.0231561 |