Reelin: Diverse roles in central nervous system development, health and disease

Int J Biochem Cell Biol. 2019 Jul;112:72-75. doi: 10.1016/j.biocel.2019.04.009. Epub 2019 Apr 22.

Abstract

Over the past 20 years the structure and function of Reelin, an extracellular glycoprotein with a role in cell migration and positioning during development has been elucidated. Originally discovered in mice exhibiting a peculiar gait and hypoplastic cerebellar tissue, Reelin is secreted from Cajal-Retzius neurons during embryonic life and has been shown to act as a stop signal, guiding migrating radial neurons in a gradient-dependent manner. Reelin carries out its function by binding to the receptors, very low-density lipoprotein receptor (VLDLR) and apolipoprotein E receptor 2 (ApoER2) resulting in the phosphorylation of the intracellular protein Disabled-1 (Dab-1) which is essential for effective Reelin signaling. Abnormalities in the RELN gene can result in multiple unusual structural outcomes including disruption of cortical layers, heterotopia, polymicrogyria and lissencephaly. Recent research has suggested a potential role for Reelin in the pathogenesis of neurological diseases such as schizophrenia, autism and Alzheimer's disease. This short review will address the current understanding of the structure and function of this protein and its emerging role in the development of neurological disorders.

Keywords: Cajal-Retzius neurons; Cortical migration; Lamination; Reelin; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / pathology
  • Animals
  • Autistic Disorder / metabolism*
  • Autistic Disorder / pathology
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Central Nervous System / metabolism*
  • Central Nervous System / pathology
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • LDL-Receptor Related Proteins / metabolism
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Receptors, LDL / metabolism
  • Schizophrenia / metabolism*
  • Schizophrenia / pathology
  • Serine Endopeptidases / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Cell Adhesion Molecules, Neuronal
  • DAB1 protein, human
  • Extracellular Matrix Proteins
  • LDL-Receptor Related Proteins
  • Nerve Tissue Proteins
  • Receptors, LDL
  • VLDL receptor
  • low density lipoprotein receptor-related protein 8
  • Serine Endopeptidases
  • reelin protein