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Galpha13 regulation of proto-Dbl signaling

Cristina Vanni1, Patrizia Mancini, Catherine Ottaviano

  • 1Laboratorio di Biologia Molecolare, Istituto G. Gaslini, Genova, Italy.

Cell Cycle (Georgetown, Tex.)
|August 28, 2007
PubMed

Insights

G protein alpha(13) (Gα13) signaling regulates Rho GTPases via proto-Dbl, a guanine nucleotide exchange factor. Gα13 activation and receptor stimulation promote proto-Dbl membrane localization and downstream signaling.

Area of Science:

  • Cellular signaling
  • Molecular biology
  • G protein-coupled receptors

Background:

  • Rho family GTPases are key regulators of intracellular signals.
  • Heterotrimeric G proteins, particularly the alpha(12/13) family, activate Rho GTPases.
  • Rho guanine nucleotide exchange factors (GEFs) with a G protein signaling-like (RGL) domain mediate this activation, but proto-Dbl, lacking an RGL domain, also links Gα(12/13) signals to Rho.

Purpose of the Study:

  • To investigate the regulation of the Rho GEF proto-Dbl by activated Gα(13) and Gα(13)-associated GPCR agonists.
  • To elucidate the downstream signaling pathways and molecular interactions involved.

Main Methods:

  • Expression of activated Gα(13) and Gα(13)-associated GPCR agonists in cells.
  • Observation of proto-Dbl translocation to the cell membrane.
  • Assessment of cell morphology changes (cell body enlargement, membrane ruffling).
  • Measurement of GTPase activation (Cdc42, RhoA) and kinase activity (JNK, p38).
  • Analysis of proto-Dbl and ezrin interaction and localization.

Main Results:

  • Activated Gα(13), but not Gα(12) or Gα(q), induced proto-Dbl translocation to the cell membrane, causing cell enlargement and membrane ruffling.
  • Gα(13)-associated GPCR agonists mimicked these effects, activating Cdc42, RhoA, JNK, and p38 kinases.
  • Both activated Gα(13) and GPCR agonists stimulated proto-Dbl interaction with ezrin, promoting ezrin translocation to the plasma membrane.

Conclusions:

  • Proto-Dbl acts as a crucial mediator linking Gα(13) signals to Rho GTPase activation and downstream effectors.
  • Gα(13)-mediated signaling regulates proto-Dbl activity and localization through ezrin interaction.
  • This study reveals a novel mechanism for Gα(13)-dependent cellular responses involving proto-Dbl and ezrin.

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