GDP-bound Gαi2 regulates spinal motor neuron differentiation through interaction with GDE2

Goran Periz, Ye Yan, Zachary T. Bitzer, Shanthini Sockanathan

Research output: Contribution to journalArticle

Abstract

Gαi proteins play major roles in the developing and mature nervous system, ranging from the control of cellular proliferation to modulating synaptic plasticity. Although best known for transducing signals from activated seven transmembrane G-protein coupled receptors (GPCRs) when bound to GTP, key cellular functions for Gαi-GDP are beginning to emerge. Here, we show that Gαi2 is expressed in motor neuron progenitors that are differentiating to form postmitotic motor neurons in the developing spinal cord. Ablation of Gαi2 causes deficits in motor neuron generation but no changes in motor neuron progenitor patterning or specification, consistent with a function for Gαi2 in regulating motor neuron differentiation. We show that Gαi2 function is mediated in part by its interaction with GDE2, a known regulator of motor neuron differentiation, and that disruption of the GDE2/Gαi2 complex in vivo causes motor neuron deficits analogous to Gαi2 ablation. Gαi2 preferentially associates with GDE2 when bound to GDP, invoking GPCR-independent functions for Gαi2 in the control of spinal motor neuron differentiation.

Original languageEnglish (US)
Pages (from-to)213-221
Number of pages9
JournalDevelopmental biology
Volume341
Issue number1
DOIs
StatePublished - May 2010

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Keywords

  • Development
  • GDE2
  • Gαi2
  • Motor neuron
  • Neuronal differentiation
  • Spinal cord

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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