Reelin: Neurodevelopmental Architect and Homeostatic Regulator of Excitatory Synapses

J Biol Chem. 2017 Jan 27;292(4):1330-1338. doi: 10.1074/jbc.R116.766782. Epub 2016 Dec 19.

Abstract

Over half a century ago, D. S. Falconer first reported a mouse with a reeling gate. Four decades later, the Reln gene was isolated and identified as the cause of the reeler phenotype. Initial studies found that loss of Reelin, a large, secreted glycoprotein encoded by the Reln gene, results in abnormal neuronal layering throughout several regions of the brain. In the years since, the known functions of Reelin signaling in the brain have expanded to include multiple postdevelopmental neuromodulatory roles, revealing an ever increasing body of evidence to suggest that Reelin signaling is a critical player in the modulation of synaptic function. In writing this review, we intend to highlight the most fundamental aspects of Reelin signaling and integrate how these various neuromodulatory effects shape and protect synapses.

Keywords: ApoE receptors; Reelin; amyloid-β (Aβ); apolipoprotein E (ApoE); neurodegeneration; neurodegenerative diseases; neurotransmitter receptor; protein-tyrosine kinase; receptor; synaptic function; tyrosine-protein kinase (tyrosine kinase).

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / genetics
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Homeostasis / physiology*
  • Humans
  • Mice
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurogenesis / physiology*
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • Signal Transduction / physiology*
  • Synapses / genetics
  • Synapses / metabolism*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Extracellular Matrix Proteins
  • Nerve Tissue Proteins
  • Serine Endopeptidases
  • reelin protein