Neuregulin induces GABAA receptor β2 subunit expression in cultured rat cerebellar granule neurons by activating multiple signaling pathways

Fang Xie, Lori T. Raetzman, Ruth E. Siegel

Research output: Contribution to journalArticlepeer-review

Abstract

The GABAA receptor β subunit is required to confer sensitivity to γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the CNS. In previous studies we demonstrated that the growth and differentiation factor neuregulin 1 (NRG1) selectively induced expression of the β2 subunit mRNA and encoded protein in rat cerebellar granule neurons in culture. In the present report we examine the signaling pathways that mediate this effect. These studies demonstrate that the effects of NRG1 on β2 subunit polypeptide expression require activation of the ErbB4 receptor tyrosine kinase; its effects are inhibited by pharmacological blockade of ErbB4 phosphorylation or reduction of receptor level with an antisense oligodeoxynucleotide. The NRG1-induced activation of ErbB4 stimulates the mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (P13K) and cyclin-dependent kinase-5 (cdk5) pathways. Pharmacological blockade of any of these pathways inhibits increased β2 subunit expression, demonstrating that all three pathways are required to mediate the effects of NRG1 on GABAA receptor subunit expression in cerebellar granule neurons. These studies provide novel information concerning the actions of NRG1 on GABAA receptor expression in the CNS.

Original languageEnglish (US)
Pages (from-to)1521-1529
Number of pages9
JournalJournal of Neurochemistry
Volume90
Issue number6
DOIs
StatePublished - Sep 2004
Externally publishedYes

Keywords

  • Cdk5 kinase
  • Cerebellar granule neurons
  • ErbB4 receptor
  • GABA receptor
  • MAP kinase
  • Neuregulin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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