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Humboldt-Universität zu Berlin | IRI Life Sciences | Scientific Events | IRI Talks | Dates | IRI-Talk - Paul Markus Müller: „Systematic Characterization of RhoGEF/RhoGAP Proteins Reveals Organization Principles of Rho GTPase Signaling“

IRI-Talk - Paul Markus Müller: „Systematic Characterization of RhoGEF/RhoGAP Proteins Reveals Organization Principles of Rho GTPase Signaling“

What
  • IRI Talk
  • Upcoming
When Feb 28, 2019 from 04:00 PM to 05:00 PM (Europe/Vienna / UTC100) iCal
Where IRI Life Sciences, Philippstr. 13, Building 18, 3rd Floor, Room 410

IRI Talk

Abstract:

Rho GTPases control cell morphogenesis and thus central processes in all eukaryotes. Their activity is regulated by 145 RhoGEF and RhoGAP multi-domain proteins in humans, to jointly organize highly localized morphodynamic cell responses. A fundamental question is how Rho activity is maintained in confined zones and how Rho GTPases and their regulators act in concert to regulate cellular morphogenesis.

Using a complete cDNA library of all full-length RhoGEFs/RhoGAPs we undertook a systems-level characterization of their functional properties. Besides their subcellular localization and interactome, we have systematically characterized their substrate specificities, by means of a live-cell FRET microscopy screen based on second generation biosensors for RhoA, Rac1, and Cdc42.

Together, our data places the Rho regulators into their functional context and enabled us to uncover emergent organization principles of Rho signaling. They localize to multiple compartments to provide positional information, are extensively interconnected to jointly coordinate their signaling networks and are widely autoinhibited to remain sensitive to local activation. Providing the first complete analysis under standardized experimental conditions, we found that RhoGAPs exhibit lower substrate specificity than RhoGEFs and may contribute to preserving local Rho activity gradients. Our study allows a bird’s-eye view of Rho signaling and provides a unique resource for future targeted and integrated studies on how RhoGEFs/RhoGAPs contextualize and spatially delimit Rho signaling.