The Central Fragment of Reelin, Generated by Proteolytic Processing in Vivo, Is Critical to Its Function during Cortical Plate Development

Yves Jossin, Nina Ignatova, Thomas Hiesberger, Joachim Herz, Catherine Lambert De Rouvroit, André M. Goffinet

Research output: Contribution to journalArticle

151 Scopus citations

Abstract

Reelin is a large extracellular protein that controls cortical development. It binds to lipoprotein receptors very-low-density lipoprotein receptor and apolipoprotein-E receptor type 2, thereby inducing phosphorylation of the adapter Dab 1. In vivo, Reelin is cleaved into three fragments, but their respective function is unknown. Here we show the following: (1) the central fragment is necessary and sufficient for receptor binding in vitro and for Dab1 phosphorylation in neuronal cultures; (2) Reelin does not bind the protocadherin cadherin-related neuronal receptor (CNR1) as reported previously; (3) Reelin and its central fragment are equally able to rescue the reeler phenotype in a slice culture assay; and (4) anti-receptor antibodies can induce Dab1 phosphorylation but do not correct the reeler phenotype in slices. These observations show that the function of Reelin is critically dependent on the central fragment generated by processing but primarily independent of interactions with CNR1 and on the N-terminal region. They also indicate that events acting in parallel to Dab 1 phosphorylation might be required for full activity.

Original languageEnglish (US)
Pages (from-to)514-521
Number of pages8
JournalJournal of Neuroscience
Volume24
Issue number2
DOIs
StatePublished - Jan 14 2004

Keywords

  • ApoER2
  • CNR1
  • Cortical development
  • Dab1
  • Reelin
  • VLDLR

ASJC Scopus subject areas

  • Neuroscience(all)

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