The Pafah1b complex interacts with the reelin receptor VLDLR

Guangcheng Zhang, Amir H. Assadi, Robert S. McNeil, Uwe Beffert, Anthony Wynshaw-Boris, Joachim Herz, Gary D. Clark, Gabriella D'Arcangelo

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Abstract

Reelin is an extracellular protein that directs the organization of cortical structures of the brain through the activation of two receptors, the very low-density lipoprotein receptor (VLDLR) and the apolipoprotein E receptor 2 (ApoER2), and the phosphorylation of Disabled-1 (Dab1). Lis1, the product of the Pafah1b1 gene, is a component of the brain platelet-activating factor acetylhydrolase 1b (Pafah1b) complex, and binds to phosphorylated Dab1 in response to Reelin. Here we investigated the involvement of the whole Pafah1b complex in Reelin signaling and cortical layer formation and found that catalytic subunits of the Pafah1b complex, Pafah1b2 and Pafah1b3, specifically bind to the NPxYL sequence of VLDLR, but not to ApoER2. Compound Pafah1b1+/-;Apoer2-/- mutant mice exhibit a reeler-like phenotype in the forebrain consisting of the inversion of cortical layers and hippocampal disorganization, whereas double Pafah1b1+/ -;Vldlr-/- mutants do not. These results suggest that a cross-talk between the Pafah1b complex and Reelin occurs downstream of the VLDLR receptor.

Original languageEnglish (US)
Article numbere252
JournalPLoS One
Volume2
Issue number2
DOIs
StatePublished - Feb 28 2007

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Zhang, G., Assadi, A. H., McNeil, R. S., Beffert, U., Wynshaw-Boris, A., Herz, J., Clark, G. D., & D'Arcangelo, G. (2007). The Pafah1b complex interacts with the reelin receptor VLDLR. PLoS One, 2(2), [e252]. https://doi.org/10.1371/journal.pone.0000252