Reelin and stk25 have opposing roles in neuronal polarization and dendritic Golgi deployment

Cell. 2010 Nov 24;143(5):826-36. doi: 10.1016/j.cell.2010.10.029.

Abstract

The Reelin ligand regulates a Dab1-dependent signaling pathway required for brain lamination and normal dendritogenesis, but the specific mechanisms underlying these actions remain unclear. We find that Stk25, a modifier of Reelin-Dab1 signaling, regulates Golgi morphology and neuronal polarization as part of an LKB1-Stk25-Golgi matrix protein 130 (GM130) signaling pathway. Overexpression of Stk25 induces Golgi condensation and multiple axons, both of which are rescued by Reelin treatment. Reelin stimulation of cultured neurons induces the extension of the Golgi into dendrites, which is suppressed by Stk25 overexpression. In vivo, Reelin and Dab1 are required for the normal extension of the Golgi apparatus into the apical dendrites of hippocampal and neocortical pyramidal neurons. This demonstrates that the balance between Reelin-Dab1 signaling and LKB1-Stk25-GM130 regulates Golgi dispersion, axon specification, and dendrite growth and provides insights into the importance of the Golgi apparatus for cell polarization.

Publication types

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

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Cell Line
  • Cell Separation
  • Cells, Cultured
  • Extracellular Matrix Proteins / metabolism*
  • Golgi Apparatus / metabolism*
  • Hippocampus / metabolism
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Nerve Tissue Proteins / metabolism*
  • Neurons / cytology*
  • Neurons / metabolism*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Rats
  • Serine Endopeptidases / metabolism*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dab1 protein, mouse
  • Extracellular Matrix Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nerve Tissue Proteins
  • Stk25 protein, mouse
  • Protein-Serine-Threonine Kinases
  • Serine Endopeptidases
  • reelin protein