Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation

Gary R. Fanger, Richard Vaillancourt, Lynn E. Heasley, Jean Pierre R Montmayeur, Gary L. Johnson, Robert A. Maue

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The mechanisms governing neuronal differentiation, including the signals underlying the induction of voltage-dependent sodium (Na+) channel expression by neurotrophic factors, which occurs independent of Ras activity, are not well understood. Therefore, Na+ channel induction was analyzed in sublines of PC12 cells stably expressing platelet-derived growth factor (PDGF) β receptors with mutations that eliminate activation of specific signaling molecules. Mutations eliminating activation of phosphatidylinositol 3-kinase (PI3K), phospholipase C(γ) (PLC(γ)), the GTPase-activating protein (GAP), and Syp phosphatase failed to diminish the induction of type II Na+ channel α-subunit mRNA and functional Na+ channel expression by PDGF, as determined by RNase protection assays and whole-cell patch clamp recording. However, mutation of juxtamembrane tyrosines that bind members of the Src family of kinases upon receptor activation inhibited the induction of functional Na+ channels while leaving the induction of type II α-subunit mRNA intact. Mutation of juxtamembrane tyrosines in combination with mutations eliminating activation of PI3K, PLC(γ), GAP, and Syp abolished the induction of type II α-subunit mRNA, suggesting that at least partially redundant signaling mechanisms mediate this induction. The differential effects of the receptor mutations on Na+ channel expression did not reflect global changes in receptor signaling capabilities, as in all of the mutant receptors analyzed, the induction of c-fos and transin mRNAs still occurred. The results reveal an important role for the Src family in the induction of Na+ channel expression and highlight the multiplicity and combinatorial nature of the signaling mechanisms governing neuronal differentiation.

Original languageEnglish (US)
Pages (from-to)89-99
Number of pages11
JournalMolecular and Cellular Biology
Volume17
Issue number1
StatePublished - Jan 1997
Externally publishedYes

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Platelet-Derived Growth Factor Receptors
Sodium Channels
PC12 Cells
Mutation
Phosphatidylinositol 3-Kinase
GTPase-Activating Proteins
Messenger RNA
Type C Phospholipases
Tyrosine
Matrix Metalloproteinase 3
src-Family Kinases
Phosphoprotein Phosphatases
Platelet-Derived Growth Factor
Nerve Growth Factors
Ribonucleases
Phosphatidylinositol 3-Kinases

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Analysis of mutant platelet-derived growth factor receptors expressed in PC12 cells identifies signals governing sodium channel induction during neuronal differentiation. / Fanger, Gary R.; Vaillancourt, Richard; Heasley, Lynn E.; Montmayeur, Jean Pierre R; Johnson, Gary L.; Maue, Robert A.

In: Molecular and Cellular Biology, Vol. 17, No. 1, 01.1997, p. 89-99.

Research output: Contribution to journalArticle

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