CRC 944: Physiology and Dynamics of Cellular Microcompartments- WP17: Establishment of endosomal membrane domains by guanine nucleotide exchange factors

Basic data for this project

Description

Rab GTPases are essential components of the conserved fusion machinery and serve as markers of membrane identity to establish microcompartments in the endomembrane system. Their precise localization is controlled by guanine nucleotide exchange factors (GEFs), which concurrently activate the cognate Rab GTPase and cause its membrane recruitment. Thus, understanding the organization and spatio-temporal coordination of intracellular traffic requires knowledge of the mechanism of RabGEF function. Current models envision that RabGEFs need to integrate several input signals and that a threshold has to be reached to trigger their function. We aim to elucidate how this process is orchestrated at a molecular level for the longin-heterodimer (LH) GEF family, which includes the Mon1/Ccz1 (MC1) and Hps1/Hps4 (BLOC3) complexes. Analysis of complex structure combined with functional studies of protein-protein and protein-lipid interactions will help us to understand how these GEFs define specific subregions in the endosomal system.