Reelin induces Erk1/2 signaling in cortical neurons through a non-canonical pathway

Gum Hwa Lee, Zinal Chhangawala, Sventja Von Daake, Jeffrey N. Savas, John R. Yates, Davide Comoletti, Gabriella D'Arcangelo

Research output: Contribution to journalArticlepeer-review

37 Scopus citations


Reelin is an extracellular protein that controls many aspects of pre- and postnatal brain development and function. The molecular mechanisms that mediate postnatal activities of Reelin are not well understood. Here, we first set out to express and purify the full length Reelin protein and a biologically active central fragment. Second, we investigated in detail the signal transduction mechanisms elicited by these purified Reelin proteins in cortical neurons. Unexpectedly, we discovered that the full-length Reelin moiety, but not the central fragment, is capable of activating Erk1/2 signaling, leading to increased p90RSK phosphorylation and the induction of immediate-early gene expression. Remarkably, Erk1/2 activation is not mediated by the canonical signal transduction pathway, involving ApoER2/VLDLR and Dab1, that mediates other functions of Reelin in early brain development. The activation of Erk1/2 signaling likely contributes to the modulation of neuronal maturation and synaptic plasticity by Reelin in the postnatal and adult brain.

Original languageEnglish (US)
Pages (from-to)20307-20317
Number of pages11
JournalJournal of Biological Chemistry
Issue number29
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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