Reelin Induces Erk1/2 Signaling in Cortical Neurons Through a
Non-canonical Pathway |
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| Authors: | Gum Hwa Lee Zinal Chhangawala Sventja von Daake Jeffrey N. Savas John R. Yates 3rd Davide Comoletti Gabriella D'Arcangelo |
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| Affiliation: | From the ‡Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854.;the §Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and ;the ¶Department of Chemical Physiology and Molecular and Cellular Neurobiology, The Scripps Research Institute, La Jolla, California 92037 |
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| Abstract: | Reelin is an extracellular protein that controls many aspects of pre- and postnatalbrain development and function. The molecular mechanisms that mediate postnatalactivities of Reelin are not well understood. Here, we first set out to express andpurify the full length Reelin protein and a biologically active central fragment.Second, we investigated in detail the signal transduction mechanisms elicited bythese purified Reelin proteins in cortical neurons. Unexpectedly, we discovered thatthe full-length Reelin moiety, but not the central fragment, is capable of activatingErk1/2 signaling, leading to increased p90RSK phosphorylation and the induction ofimmediate-early gene expression. Remarkably, Erk1/2 activation is not mediated by thecanonical signal transduction pathway, involving ApoER2/VLDLR and Dab1, that mediatesother functions of Reelin in early brain development. The activation of Erk1/2signaling likely contributes to the modulation of neuronal maturation and synapticplasticity by Reelin in the postnatal and adult brain. |
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| Keywords: | Cell Culture Cell Signaling Extracellular Signal-regulated Kinase (ERK) Neurodevelopment Signal Transduction |
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