The Pafah1b complex interacts with the Reelin receptor VLDLR

The Cain Foundation Laboratories, Texas Children's Hospital, Houston, Texas, United States of America.
PLoS ONE (Impact Factor: 3.23). 02/2007; 2(2):e252. DOI: 10.1371/journal.pone.0000252
Source: PubMed


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.

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Available from: Gabriella D'Arcangelo, Jul 02, 2014
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    • "Since the radial glial scaffold is also severely perturbed in these reelin signaling hippocampal mutants (Forster et al., 2002; Weiss et al., 2003), the contribution of this signaling pathway to different aspects of neuronal migration is certainly multiple, and this is very likely to be a convergence point between non-cell-autonomous and cell-autonomous regulators. For example, secreted reelin can control radial glial scaffold development, however it can also influence interaction of phosphorylated Dab1 with Lis1 within migrating neurons (Assadi et al., 2003; Zhang et al., 2007). The severe phenotype observed in Lis1 mutants could also be the consequence of a deregulation of the reelin signaling pathway within these neurons themselves. "
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    • "Reelin induces binding of Lis1, encoded by the Pafah1b1 gene, to Dab1, an essential component of the reelin signaling cascade. The Pafah1b complex interacts with the reelin receptor VLDLR, and compound mutant mice deficient for Pafah1b1 and apoER2 exhibit a reeler like phenotype (Zhang et al. 2007). Migrating interneurons in Lis ± mice exhibit reduced leading process stability and reduced a-tubulin acetylation in leading processes (Gopal et al. 2010). "
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