title: Reelin induces Erk1/2 signaling in cortical neurons through a non-canonical pathway.
abstract: 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.
authors.affiliation: From the Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854.
authors.forename: Gum Hwa
authors.initials: GH
authors.lastname: Lee
authors.affiliation: the Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and.
authors.forename: Zinal
authors.initials: Z
authors.lastname: Chhangawala
authors.affiliation: the Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and.
authors.forename: Sventja
authors.initials: S
authors.lastname: von Daake
authors.affiliation: the Department of Chemical Physiology and Molecular and Cellular Neurobiology, The Scripps Research Institute, La Jolla, California 92037.
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Savas
authors.affiliation: the Department of Chemical Physiology and Molecular and Cellular Neurobiology, The Scripps Research Institute, La Jolla, California 92037.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: the Department of Neuroscience and Cell Biology, Rutgers Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, and.
authors.forename: Davide
authors.initials: D
authors.lastname: Comoletti
authors.affiliation: From the Department of Cell Biology and Neuroscience, Rutgers, the State University of New Jersey, Piscataway, New Jersey 08854, darcangelo@biology.rutgers.edu.
authors.forename: Gabriella
authors.initials: G
authors.lastname: D'Arcangelo
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D017781:Genes, Immediate-Early; D006579:Heterozygote; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011973:Receptors, LDL / Q000378:metabolism; D000091042:Reelin Protein; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C103773:Dab1 protein, mouse; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011973:Receptors, LDL; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; D051057:Proto-Oncogene Proteins c-akt; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases
keywords: Cell Culture; Cell Signaling; Extracellular Signal-regulated Kinase (ERK); Neurodevelopment; Signal Transduction