The Pafah1b complex interacts with the reelin receptor VLDLR.
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.
Pubmed ID: 17330141 RIS Download
1-Alkyl-2-acetylglycerophosphocholine Esterase | Amino Acid Motifs | Amino Acid Sequence | Animals | COS Cells | Catalytic Domain | Cell Adhesion Molecules, Neuronal | Cell Line | Cercopithecus aethiops | Cerebral Cortex | Extracellular Matrix Proteins | Hippocampus | Humans | LDL-Receptor Related Proteins | Lissencephaly | Mice | Mice, Inbred C57BL | Mice, Knockout | Mice, Neurologic Mutants | Microtubule-Associated Proteins | Molecular Sequence Data | Nerve Tissue Proteins | Protein Binding | Protein Interaction Mapping | Receptors, Cell Surface | Receptors, LDL | Receptors, Lipoprotein | Recombinant Fusion Proteins | Serine Endopeptidases | Signal Transduction