β-adrenergic and fibroblast growth factor receptors induce neuronal process outgrowth through different mechanisms

John H. Kwon, Daniela M. Vogt Weisenhorn, Martha Downen, Kesan Ruan, Linda Roback, Harish Joshi, Bruce H. Wainer

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The mechanisms that initiate and direct neuronal process formation remain poorly understood. We have recently described a neuronal progenitor cell line, AS583-8.E4.22 (AS583-8) which undergoes neurite formation in response to β2-adrenergic and basic fibroblast growth factor (bFGF) receptor activation. In the present study, a comparison of these responses revealed that isoproterenol (ISO), a β-adrenergic receptor agonist, induces multiple, highly branched processes within 30 min while bFGF induces fewer, unbranched processes within 24 h. In contrast to the ISO response, bFGF induces mitogen-activated protein kinase activation and c-fos expression in the cell line and results in neurite outgrowth that is dependent on new mRNA and protein synthesis. Two-dimensional isoelectric focusing-sodium dodecyl sulphate-polyacrylamide gel electrophoresis of cytoskeletal preparations revealed different patterns following ISO vs. bFGF exposure suggesting selective changes in protein expression and/or post-translational modifications. Immunoblot analysis of these preparations for β-tubulin, tyrosinated α-tubulin and acetylated α-tubulin also revealed different patterns following each type of treatment. Follow-up confocal microscopy revealed that following ISO, the distribution of tyrosinated tubulin extends to the distal ends of processes whereas acetylated α-tubulin is diminished within distal ends. This pattern has been reported to be associated with enhanced microtubule dynamics, a state in which process outgrowth is facilitated. In contrast, following bFGF treatment the distributions of tyrosinated and acetylated α-tubulin were identical, a state associated with a diminution of microtubule dynamics. These results, a different time course of neurite formation, dependency on new gene expression and differential expression and cellular distribution of major cytoskeleton proteins suggest that neurite outgrowth induced by ISO vs. bFGF is mediated by two distinct intracellular effector mechanisms in AS583-8 cells. In addition, studies, using the differential distribution of post-translational modified α-tubulins in neurites of primary neuronal cultures as marker for the two distinct processes of neurite formation suggest, that similar mechanisms are present in vivo. Therefore, the AS583-8 cell line provides a useful model to study these signalling mechanisms that couple neurotransmitter and growth factor receptor activation to the cytoskeletal changes that mediate neurite formation.

Original languageEnglish (US)
Pages (from-to)2776-2789
Number of pages14
JournalEuropean Journal of Neuroscience
Volume10
Issue number9
DOIs
StatePublished - Dec 1 1998

Fingerprint

Fibroblast Growth Factor Receptors
Tubulin
Adrenergic Agents
Fibroblast Growth Factor 2
Neurites
Isoproterenol
Cell Line
Microtubules
Adrenergic Agonists
Proteins
Growth Factor Receptors
Isoelectric Focusing
Post Translational Protein Processing
Neuronal Outgrowth
Mitogen-Activated Protein Kinases
Cytoskeleton
Confocal Microscopy
Sodium Dodecyl Sulfate
Neurotransmitter Agents
Polyacrylamide Gel Electrophoresis

Keywords

  • β-adrenergic receptor
  • Basic fibroblast growth factor
  • Cell line
  • Fibroblast growth factor receptor
  • Neurite outgrowth
  • Tubulin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

β-adrenergic and fibroblast growth factor receptors induce neuronal process outgrowth through different mechanisms. / Kwon, John H.; Vogt Weisenhorn, Daniela M.; Downen, Martha; Ruan, Kesan; Roback, Linda; Joshi, Harish; Wainer, Bruce H.

In: European Journal of Neuroscience, Vol. 10, No. 9, 01.12.1998, p. 2776-2789.

Research output: Contribution to journalArticle

Kwon, John H. ; Vogt Weisenhorn, Daniela M. ; Downen, Martha ; Ruan, Kesan ; Roback, Linda ; Joshi, Harish ; Wainer, Bruce H. / β-adrenergic and fibroblast growth factor receptors induce neuronal process outgrowth through different mechanisms. In: European Journal of Neuroscience. 1998 ; Vol. 10, No. 9. pp. 2776-2789.
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