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.
Zhang
Guangcheng
G
The Cain Foundation Laboratories, Texas Children's Hospital, Houston, Texas, United States of America.
Assadi
Amir H
AH
McNeil
Robert S
RS
Beffert
Uwe
U
Wynshaw-Boris
Anthony
A
Herz
Joachim
J
Clark
Gary D
GD
D'Arcangelo
Gabriella
G
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D020134:Catalytic Domain; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology*; D002460:Cell Line; D002540:Cerebral Cortex / Q000002:abnormalities*; D002522:Chlorocebus aethiops; D016326:Extracellular Matrix Proteins / Q000502:physiology*; D006624:Hippocampus / Q000002:abnormalities*; D006801:Humans; D026502:LDL-Receptor Related Proteins; D054082:Lissencephaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008869:Microtubule-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D011956:Receptors, Cell Surface / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018110:Receptors, Lipoprotein / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D026502:LDL-Receptor Related Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011973:Receptors, LDL; D018110:Receptors, Lipoprotein; D011993:Recombinant Fusion Proteins; D000091042:Reelin Protein; C036053:VLDL receptor; C098773:low density lipoprotein receptor-related protein 8; C469363:reelin receptor; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C000607175:PAFAH1b2 protein, mouse; C000607176:PAFAH1b3 protein, mouse; C513190:Pafah1b1 protein, mouse; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases