Ephrin-A5 suppresses neurotrophin evoked neuronal motility, ERK activation and gene expression

peer-reviewed
Erstveröffentlichung
2011-10-11Autoren
Meier, Christin
Anastasiadou, Sofia
Knöll, Bernd
Wissenschaftlicher Artikel
Erschienen in
PLoS ONE ; 6 (2011), 10. - Art.-Nr. e26089. - eISSN 1932-6203
Link zur Originalveröffentlichung
https://dx.doi.org/10.1371/journal.pone.0026089Fakultäten
Medizinische FakultätInstitutionen
Institut für Physiologische ChemieDokumentversion
Veröffentlichte Version (Verlags-PDF)Zusammenfassung
During brain development, growth cones respond to attractive and repulsive axon guidance cues. How growth cones integrate guidance instructions is poorly understood. Here, we demonstrate a link between BDNF (brain derived neurotrophic factor), promoting axonal branching and ephrin-A5, mediating axonal repulsion via Eph receptor tyrosine kinase activation. BDNF enhanced growth cone filopodial dynamics and neurite branching of primary neurons. We show that ephrin-A5 antagonized this BDNF-evoked neuronal motility. BDNF increased ERK phosphorylation (P-ERK) and nuclear ERK entry. Ephrin-A5 suppressed BDNF-induced ERK activity and might sequester P-ERK in the cytoplasm. Neurotrophins are well established stimulators of a neuronal immediate early gene (IEG) response. This is confirmed in this study by e.g. c-fos, Egr1 and Arc upregulation upon BDNF application. This BDNF-evoked IEG response required the transcription factor SRF (serum response factor). Notably, ephrin-A5 suppressed a BDNF-evoked neuronal IEG response, suggesting a role of Eph receptors in modulating gene expression. In opposite to IEGs, long-term ephrin-A5 application induced cytoskeletal gene expression of tropomyosin and actinin. To uncover specific Eph receptors mediating ephrin-As impact on neurotrophin signaling, EphA7 deficient mice were analyzed. In EphA7 deficient neurons alterations in growth cone morphology were observed. However, ephrin-A5 still counteracted neurotrophin signaling suggesting that EphA7 is not required for ephrin and BDNF crosstalk. In sum, our data suggest an interaction of ephrin-As and neurotrophin signaling pathways converging at ERK signaling and nuclear gene activity. As ephrins are involved in development and function of many organs, such modulation of receptor tyrosine kinase signaling and gene expression by Ephs might not be limited to the nervous system.
DFG-Projekt uulm
Transkriptionale Regulation des Nervenwachstums in Entwicklung und Pathologie / DFG / Emmy Noether-Nachwuchsgruppen / 15171843 [KN543/2-1]
SFB 446 Teilprojekt B19 / Die Rolle von Histon Deacetylasen (HDACs) bei der Motilität neuronaler Zellen / DFG / 5481932
SFB 446 Teilprojekt B19 / Die Rolle von Histon Deacetylasen (HDACs) bei der Motilität neuronaler Zellen / DFG / 5481932
Wird ergänzt durch
https://journals.plos.org/plosone/article/file?type=supplementary&id=10.1371/journal.pone.0026089.s001https://journals.plos.org/plosone/article/file?type=supplementary&id=10.1371/journal.pone.0026089.s002
https://journals.plos.org/plosone/article/file?type=supplementary&id=10.1371/journal.pone.0026089.s003
https://journals.plos.org/plosone/article/file?type=supplementary&id=10.1371/journal.pone.0026089.s004
Schlagwörter
[GND]: Nervenzelle | Axon | Hippocampus | Genexpression | Zellskelett[LCSH]: Neurons | Gene expression | Cytoskeleton
[Freie Schlagwörter]: ERK signaling cascade | Neurites | Axon guidance | Axon guidance receptors
[DDC Sachgruppe]: DDC 570 / Life sciences
Metadata
Zur LanganzeigeDOI & Zitiervorlage
Nutzen Sie bitte diesen Identifier für Zitate & Links: http://dx.doi.org/10.18725/OPARU-48913
Meier, Christin; Anastasiadou, Sofia; Knöll, Bernd (2023): Ephrin-A5 suppresses neurotrophin evoked neuronal motility, ERK activation and gene expression. Open Access Repositorium der Universität Ulm und Technischen Hochschule Ulm. http://dx.doi.org/10.18725/OPARU-48913
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