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5-HT(1A) receptors transactivate the platelet-derived growth factor receptor type beta in neuronal cells

Jeff S Kruk1, Maryam S Vasefi, Hui Liu

  • 1Department of Biology, University of Waterloo, Canada.

Cellular Signalling
|September 26, 2012
PubMed

Insights

Serotonin (5-HT) receptors transactivate platelet-derived growth factor (PDGF) β receptors in neurons, revealing a novel signaling pathway. This crosstalk links the serotonergic system with growth factor signaling in neuronal cells.

Area of Science:

  • Neuroscience
  • Cell Signaling
  • Molecular Biology

Background:

  • Growth factor receptors can activate without ligands via G-protein coupled receptor (GPCR) transactivation.
  • Serotonin (5-HT) receptors are known to transactivate platelet-derived growth factor (PDGF) β receptors in smooth muscle cells.
  • The occurrence of similar pathways in neuronal cells remains largely uncharacterized.

Purpose of the Study:

  • To investigate whether serotonin (5-HT) can transactivate PDGF β receptors in neuronal cells.
  • To elucidate the signaling mechanisms and downstream effects of this transactivation pathway.
  • To explore the crosstalk between serotonergic and growth factor signaling in neurons.

Main Methods:

  • Utilized SH-SY5Y neuroblastoma cells and primary cortical neurons.
  • Assessed PDGFβ receptor phosphorylation in response to 5-HT treatment.
  • Investigated the involvement of 5-HT(1A) receptors, pertussis toxin, Src tyrosine kinase, phospholipase C, and intracellular calcium signaling.
  • Examined ERK1/2 phosphorylation to understand downstream signaling events.

Main Results:

  • 5-HT transiently increased PDGFβ receptor phosphorylation in SH-SY5Y cells and primary cortical neurons via 5-HT(1A) receptors in a time- and dose-dependent manner.
  • The transactivation pathway was sensitive to pertussis toxin and dependent on Src tyrosine kinase, phospholipase C, and intracellular calcium.
  • Unlike other studies, 5-HT treatment in SH-SY5Y cells led to PDGFβ receptor-independent ERK1/2 phosphorylation.

Conclusions:

  • Serotonin (5-HT) transactivates PDGFβ receptors in neuronal cells through a pathway involving 5-HT(1A) receptors, pertussis toxin-sensitive G-proteins, Src kinase, PLC, and calcium.
  • This study reveals a novel signaling link between the serotonergic system and growth factor signaling in neurons.
  • The PDGFβ receptor-independent activation of ERK1/2 by 5-HT highlights unique signaling crosstalk in neuroblastoma cells.

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