"G-Protein activation was predominantly seen as a "relay station” integrating extracellular signals via membrane spanning receptors with intracellular responses. The central role of this activation in cell responses to hormones and neurotransmitters makes G-proteins a major target for a wide range of powerful pharmaceuticals in humans. However, we now believe that a cellular mechanism exists which can activate these key proteins without extracellular stimulation. This fundamental insight could help gaining better understanding of disease mechanisms and will aid the development of novel therapies ” comments Dr. Knoblich.
Published in tomorrow’s issue of Cell (Vol. 107/2). the work by Knoblich describes a role for the cellular protein Pins (Partner of Inscuteable) in the localised activation of G-proteins in asymmetrically dividing cells of the developing Drosophila nervous system. Autonomous activation of G-proteins is shown to be part of a synchronised interaction of several proteins in differentiating neuroblasts. The receptor-independent activation of G-proteins is believed to support cellular polarity not only in neuroblasts but also in precursor cells of sensory organs (SOPs). Such establishment and maintenance of cellular polarity is essential for correct differentiation of these cells after delamination from adjacent tissue.
Previous work by Stephen Lanier and colleagues at the Medical University of South Carolina showed that Pins are conserved in humans and can activate G-proteins under controlled in vitro conditions. Taken together with the in vivo data from Drosophila reported here it is believed that receptor-independent G-protein activation plays an important role in human cell differentiation.
The Research Institute of Molecular Pathology – IMP (www.imp.univie.ac.at) is the "Life Science Think Tank" of the Boehringer Ingelheim group of companies, headquartered in Ingelheim, Germany, one of the 20 leading pharmaceutical corporations in the world. Advised by an international Scientific Advisory Board which includes this years Nobel Laureate Tim Hunt (UK), the 120 scientists at the IMP are engaged in basic research on subjects including cell cycle control and cell differentiation. The partnership with Boehringer Ingelheim allows for rapid technology transfer and development of new therapies based on the fundamental work pursued at the IMP.
Contact:
Dr. Heidemarie Hurtl, T +43 1 79730-358, E hurtl@imp.univie.ac.at
Dr. Jürgen Knoblich T +43 1 79730-451, E knoblich@nt.imp.univie.ac.at
Journal
Cell