Reelin signaling modulates GABAB receptor function in the neocortex

Mohammad I.K. Hamad, Abdalrahim Jbara, Obada Rabaya, Petya Petrova, Solieman Daoud, Nesrine Melliti, Maurice Meseke, David Lutz, Elisabeth Petrasch-Parwez, Jan Claudius Schwitalla, Melanie D. Mark, Stefan Herlitze, Gebhard Reiss, Joachim Herz, Eckart Förster

Research output: Contribution to journalArticle

Abstract

Reelin is a protein that is best known for its role in controlling neuronal layer formation in the developing cortex. Here, we studied its role for post-natal cortical network function, which is poorly explored. To preclude early cortical migration defects caused by Reelin deficiency, we used a conditional Reelin knock-out (RelncKO) mouse, and induced Reelin deficiency post-natally. Induced Reelin deficiency caused hyperexcitability of the neocortical network in vitro and ex vivo. Blocking Reelin binding to its receptors ApoER2 and VLDLR resulted in a similar effect. Hyperexcitability in RelncKO organotypic slice cultures could be rescued by co-culture with wild-type organotypic slice cultures. Moreover, the GABAB receptor (GABABR) agonist baclofen failed to activate and the antagonist CGP35348 failed to block GABABRs in RelncKO mice. Immunolabeling of RelncKO cortical slices revealed a reduction in GABABR1 and GABABR2 surface expression at the plasma membrane and western blot of RelncKO cortical tissue revealed decreased phosphorylation of the GABABR2 subunit at serine 892 and increased phosphorylation at serine 783, reflecting receptor deactivation and proteolysis. These data show a role of Reelin in controlling early network activity, by modulating GABABR function. (Figure presented.).

Original languageEnglish (US)
JournalJournal of Neurochemistry
DOIs
StateAccepted/In press - Jan 1 2020

Keywords

  • ApoER2 and VLDLR
  • calcium imaging
  • GABAB receptors
  • network activity
  • Reelin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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  • Cite this

    Hamad, M. I. K., Jbara, A., Rabaya, O., Petrova, P., Daoud, S., Melliti, N., Meseke, M., Lutz, D., Petrasch-Parwez, E., Schwitalla, J. C., Mark, M. D., Herlitze, S., Reiss, G., Herz, J., & Förster, E. (Accepted/In press). Reelin signaling modulates GABAB receptor function in the neocortex. Journal of Neurochemistry. https://doi.org/10.1111/jnc.14990