Functional analysis of the RhoGEF protein Solo in invasive cell migration

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The dynamic remodeling of the actin and microtubule cytoskeleton by Rho GTPase signaling is required for various cellular processes such as cell motility and vesicular trafficking in endo- and exocytosis. Regulation of Rho proteins is coordinated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs) that turn on and off GTPase signaling, respectively. Despite their importance in Rho regulation, the specific GEFs and GAPs involved in the spatial and temporal control of Rho GTPase activity are still largely elusive. We recently identified the RhoGAP protein DLC3 to regulate membrane trafficking at the level of the Golgi and endocytic recycling compartments by local RhoA regulation. To identify Rho-specific GEF proteins that balance DLC3 GAP activity, we set up an image-based high-content microscopy RNAi screen using the Golgi complex as a sensor. We identified the RhoGEF protein Solo/Arhgef40 as a potential DLC3 counterpart in Rho regulation. The aim of this study is to explore the cellular function of Solo in the regulation of cytoskeletal remodeling and membrane trafficking and, based on our preliminary data, its contribution to invasive cell migration. By pin-pointing the subcellular sites of Solo action, we further aim to unveil its molecular connection with DLC3 in the spatial regulation of specific Rho GTPase pools.