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Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2

Item Type:Article
Title:Reeler/Disabled-like disruption of neuronal migration in knockout mice lacking the VLDL receptor and ApoE receptor 2
Creators Name:Trommsdorff, M. and Gotthardt, M. and Hiesberger, T. and Shelton, J. and Stockinger, W. and Nimpf, J. and Hammer, R.E. and Richardson, J.A. and Herz, J.
Abstract:Layering of neurons in the cerebral cortex and cerebellum requires Reelin, an extracellular matrix protein, and mammalian Disabled (mDab1), a cytosolic protein that activates tyrosine kinases. Here, we report the requirement for two other proteins, cell surface receptors termed very low density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2). Both receptors can bind mDab1 on their cytoplasmic tails and are expressed in cortical and cerebellar layers adjacent to layers that express Reelin. mDab1 expression is upregulated in knockout mice that lack both VLDLR and ApoER2. Inversion of cortical layers and absence of cerebellar foliation in these animals precisely mimic the phenotype of mice lacking Reelin or mDab1. These findings suggest that VLDLR and ApoER2 participate in transmitting the extracellular Reelin signal to intracellular signaling processes initiated by mDab1.
Keywords:Amino Acid Sequence, Neuronal Cell Adhesion Molecules, Cell Line, Cell Movement, Cerebral Cortex, Dendrites, Extracellular Matrix Proteins, Molecular Sequence Data, Nerve Tissue Proteins, Purkinje Cells, LDL Receptors, Lipoprotein Receptors, Recombinant Fusion Proteins, Serine Endopeptidases, Up-Regulation, Animals, Mice
Source:Cell
ISSN:0092-8674
Publisher:Cell Press (U.S.A.)
Volume:97
Number:6
Page Range:689-701
Date:11 June 1999
Official Publication:https://doi.org/10.1016/S0092-8674(00)80782-5
PubMed:View item in PubMed

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