The Pafah1b Complex Interacts with the Reelin Receptor VLDLR
Open Access
- 28 February 2007
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 2 (2) , e252
- https://doi.org/10.1371/journal.pone.0000252
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.Keywords
This publication has 42 references indexed in Scilit:
- Absence of Fyn and Src Causes a Reeler-Like PhenotypeJournal of Neuroscience, 2005
- LIS1 RNA interference blocks neural stem cell division, morphogenesis, and motility at multiple stagesThe Journal of cell biology, 2005
- Homozygous Deletion of the Very Low Density Lipoprotein Receptor Gene Causes Autosomal Recessive Cerebellar Hypoplasia with Cerebral Gyral SimplificationAmerican Journal of Human Genetics, 2005
- Modulation of Synaptic Plasticity and Memory by Reelin Involves Differential Splicing of the Lipoprotein Receptor Apoer2Neuron, 2005
- Essential Role of the Apolipoprotein E Receptor-2 in Sperm DevelopmentJournal of Biological Chemistry, 2003
- Autosomal recessive lissencephaly with cerebellar hypoplasia is associated with human RELN mutationsNature Genetics, 2000
- Interactions of the Low Density Lipoprotein Receptor Gene Family with Cytosolic Adaptor and Scaffold Proteins Suggest Diverse Biological Functions in Cellular Communication and Signal TransductionJournal of Biological Chemistry, 2000
- The Reelin Receptor ApoER2 Recruits JNK-interacting Proteins-1 and -2Journal of Biological Chemistry, 2000
- Direct Binding of Reelin to VLDL Receptor and ApoE Receptor 2 Induces Tyrosine Phosphorylation of Disabled-1 and Modulates Tau PhosphorylationNeuron, 1999
- Reelin Is a Ligand for Lipoprotein ReceptorsNeuron, 1999