Reelin promotes hippocampal dendrite development through the VLDLR/ApoER2-Dab1 pathway

Neuron. 2004 Jan 8;41(1):71-84. doi: 10.1016/s0896-6273(03)00819-5.

Abstract

Reelin is a secreted glycoprotein that regulates neuronal positioning in cortical brain structures through the VLDLR and ApoER2 receptors and the adaptor protein Dab1. In addition to cellular disorganization, dendrite abnormalities are present in the brain of reeler mice lacking Reelin. It is unclear whether these defects are due primarily to cellular ectopia or the absence of Reelin. Here we examined dendrite development in the hippocampus of normal and mutant mice and in dissociated cultures. We found that dendrite complexity is severely reduced in homozygous mice deficient in Reelin signaling both in vivo and in vitro, and it is also reduced in heterozygous mice in the absence of cellular ectopia. Addition of Reelin interfering antibodies, receptor antagonists, and Dab1 phosphorylation inhibitors prevented dendrite outgrowth from normal neurons, whereas addition of recombinant Reelin rescued the deficit in reeler cultures. Thus, the same signaling pathway controls both neuronal migration and dendrite maturation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism
  • Cell Adhesion Molecules, Neuronal / physiology*
  • Cells, Cultured
  • Dendrites / physiology*
  • Extracellular Matrix Proteins / metabolism
  • Extracellular Matrix Proteins / physiology*
  • Hippocampus / growth & development*
  • LDL-Receptor Related Proteins
  • Mice
  • Mice, Knockout
  • Mice, Neurologic Mutants
  • Mice, Transgenic
  • Microtubule-Associated Proteins / metabolism
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology*
  • Neurons / physiology
  • Receptors, LDL / metabolism*
  • Receptors, Lipoprotein / metabolism*
  • Serine Endopeptidases / metabolism
  • Serine Endopeptidases / physiology*
  • Signal Transduction / physiology

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • LDL-Receptor Related Proteins
  • Microtubule-Associated Proteins
  • Mtap2 protein, mouse
  • Nerve Tissue Proteins
  • Receptors, LDL
  • Receptors, Lipoprotein
  • VLDL receptor
  • low density lipoprotein receptor-related protein 8
  • Serine Endopeptidases
  • reelin protein