ERK MAP kinase activation is required for acetylcholine receptor inducing activity-induced increase in all five acetylcholine receptor subunit mRNAs as well as synapse-specific expression of acetylcholine receptor ε- transgene

Jutong Si, Lin Mei

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The AChR is a pentamer of four different subunits in a stoichiometry of α2βγδ in embryonic and α2βεδ in adult animals. Transcription of AChR subunit genes is most active in synaptic nuclei in adult skeletal muscle cells, and is regulated by neural factors such as ARIA. We report here that ARIA up-regulated specifically the expression of all five AChR subunits in C2C12 cells. The mRNA level of erbB2, erbB3, rapsyn, MUSK, SHP-2 and β- actin remained unchanged in response to ARIA stimulation in C2C12 cells. The ARIA-induced increase in AChR subunit expression in C2C12 cells was inhibited by the erbB kinase inhibitor tyrphostin AG1478 and the MEK inhibitor PD98059, but not by the PI3 kinase inhibitor wortmannin, suggesting an important role of the erbB protein tyrosine kinases and MAP kinase in the regulation of the expression of the five different AChR subunits. To determine the signaling pathways in vivo, we studied the expression of reporter genes driven by the ε-promoter in injected muscles. The in vivo expression of the ε-transgene was inhibited by co-expression of dominant negative mutants of key components in the MAP kinase pathway including ras, raf and MEK, but not the dominant negative mutant of PI3 kinase. These results suggest that ERK MAP kinase activation is required for ARIA-induced increase in all five AChR subunit mRNAs as well as synapse-specific expression of AChR ε-transgene.

Original languageEnglish (US)
Pages (from-to)18-27
Number of pages10
JournalMolecular Brain Research
Volume67
Issue number1
DOIs
StatePublished - Apr 6 1999

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Mitogen-Activated Protein Kinase Kinases
Extracellular Signal-Regulated MAP Kinases
Cholinergic Receptors
Transgenes
Synapses
Phosphatidylinositol 3-Kinases
Protein-Tyrosine Kinases
Messenger RNA
Phosphotransferases
Reporter Genes
Muscle Cells
Actins
Skeletal Muscle
Muscles
Genes

Keywords

  • ARIA
  • Acetylcholine receptor
  • MAP kinase
  • Synapse
  • Transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Cite this

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title = "ERK MAP kinase activation is required for acetylcholine receptor inducing activity-induced increase in all five acetylcholine receptor subunit mRNAs as well as synapse-specific expression of acetylcholine receptor ε- transgene",
abstract = "The AChR is a pentamer of four different subunits in a stoichiometry of α2βγδ in embryonic and α2βεδ in adult animals. Transcription of AChR subunit genes is most active in synaptic nuclei in adult skeletal muscle cells, and is regulated by neural factors such as ARIA. We report here that ARIA up-regulated specifically the expression of all five AChR subunits in C2C12 cells. The mRNA level of erbB2, erbB3, rapsyn, MUSK, SHP-2 and β- actin remained unchanged in response to ARIA stimulation in C2C12 cells. The ARIA-induced increase in AChR subunit expression in C2C12 cells was inhibited by the erbB kinase inhibitor tyrphostin AG1478 and the MEK inhibitor PD98059, but not by the PI3 kinase inhibitor wortmannin, suggesting an important role of the erbB protein tyrosine kinases and MAP kinase in the regulation of the expression of the five different AChR subunits. To determine the signaling pathways in vivo, we studied the expression of reporter genes driven by the ε-promoter in injected muscles. The in vivo expression of the ε-transgene was inhibited by co-expression of dominant negative mutants of key components in the MAP kinase pathway including ras, raf and MEK, but not the dominant negative mutant of PI3 kinase. These results suggest that ERK MAP kinase activation is required for ARIA-induced increase in all five AChR subunit mRNAs as well as synapse-specific expression of AChR ε-transgene.",
keywords = "ARIA, Acetylcholine receptor, MAP kinase, Synapse, Transcription",
author = "Jutong Si and Lin Mei",
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T1 - ERK MAP kinase activation is required for acetylcholine receptor inducing activity-induced increase in all five acetylcholine receptor subunit mRNAs as well as synapse-specific expression of acetylcholine receptor ε- transgene

AU - Si, Jutong

AU - Mei, Lin

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N2 - The AChR is a pentamer of four different subunits in a stoichiometry of α2βγδ in embryonic and α2βεδ in adult animals. Transcription of AChR subunit genes is most active in synaptic nuclei in adult skeletal muscle cells, and is regulated by neural factors such as ARIA. We report here that ARIA up-regulated specifically the expression of all five AChR subunits in C2C12 cells. The mRNA level of erbB2, erbB3, rapsyn, MUSK, SHP-2 and β- actin remained unchanged in response to ARIA stimulation in C2C12 cells. The ARIA-induced increase in AChR subunit expression in C2C12 cells was inhibited by the erbB kinase inhibitor tyrphostin AG1478 and the MEK inhibitor PD98059, but not by the PI3 kinase inhibitor wortmannin, suggesting an important role of the erbB protein tyrosine kinases and MAP kinase in the regulation of the expression of the five different AChR subunits. To determine the signaling pathways in vivo, we studied the expression of reporter genes driven by the ε-promoter in injected muscles. The in vivo expression of the ε-transgene was inhibited by co-expression of dominant negative mutants of key components in the MAP kinase pathway including ras, raf and MEK, but not the dominant negative mutant of PI3 kinase. These results suggest that ERK MAP kinase activation is required for ARIA-induced increase in all five AChR subunit mRNAs as well as synapse-specific expression of AChR ε-transgene.

AB - The AChR is a pentamer of four different subunits in a stoichiometry of α2βγδ in embryonic and α2βεδ in adult animals. Transcription of AChR subunit genes is most active in synaptic nuclei in adult skeletal muscle cells, and is regulated by neural factors such as ARIA. We report here that ARIA up-regulated specifically the expression of all five AChR subunits in C2C12 cells. The mRNA level of erbB2, erbB3, rapsyn, MUSK, SHP-2 and β- actin remained unchanged in response to ARIA stimulation in C2C12 cells. The ARIA-induced increase in AChR subunit expression in C2C12 cells was inhibited by the erbB kinase inhibitor tyrphostin AG1478 and the MEK inhibitor PD98059, but not by the PI3 kinase inhibitor wortmannin, suggesting an important role of the erbB protein tyrosine kinases and MAP kinase in the regulation of the expression of the five different AChR subunits. To determine the signaling pathways in vivo, we studied the expression of reporter genes driven by the ε-promoter in injected muscles. The in vivo expression of the ε-transgene was inhibited by co-expression of dominant negative mutants of key components in the MAP kinase pathway including ras, raf and MEK, but not the dominant negative mutant of PI3 kinase. These results suggest that ERK MAP kinase activation is required for ARIA-induced increase in all five AChR subunit mRNAs as well as synapse-specific expression of AChR ε-transgene.

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KW - Acetylcholine receptor

KW - MAP kinase

KW - Synapse

KW - Transcription

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