Role of the integrin-linked kinase (ILK) in determining neuronal polarity

Dev Biol. 2007 Jun 15;306(2):457-68. doi: 10.1016/j.ydbio.2007.03.019. Epub 2007 Mar 20.

Abstract

The establishment of axon-dendrite polarity in mammalian neurons has recently been shown to involve the kinases Akt and GSK-3beta. Here we report the function of the integrin-linked kinase (ILK) in neuronal polarization. ILK distribution is differential: with more of it present in the axonal tips than that in the dendritic tips of a polarized neuron. Inactivation of ILK by chemical inhibitors, a kinase-inactive mutant or siRNAs inhibited axon formation, whereas a kinase hyperactive ILK mutant induced the formation of multiple axons. Biochemical studies indicate that ILK is upstream of Akt and GSK-3beta. Manipulations of multiple intracellular components indicate that ILK is functionally upstream of Akt and GSK-3beta but downstream of PI3K in neuronal polarity. These results reveal a key role of ILK in the formation of neuronal polarity and suggest a signaling pathway important for neuronal polarity.

Publication types

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

MeSH terms

  • Animals
  • Axons / metabolism
  • Body Patterning*
  • DNA / metabolism
  • Dendritic Cells / cytology
  • Glycogen Synthase Kinase 3 / metabolism
  • Glycogen Synthase Kinase 3 beta
  • Hippocampus / metabolism
  • Humans
  • Models, Biological
  • Neurons / metabolism
  • Neurons / pathology*
  • Protein-Serine-Threonine Kinases / genetics*
  • RNA, Small Interfering / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • RNA, Small Interfering
  • DNA
  • integrin-linked kinase
  • GSK3B protein, human
  • Glycogen Synthase Kinase 3 beta
  • Gsk3b protein, rat
  • Protein-Serine-Threonine Kinases
  • Glycogen Synthase Kinase 3