P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils

ABSTRACT G-protein-coupled receptors (GPCRs) regulate the organisation of the actin cytoskeleton by activating the Rac subfamily of small GTPases. The guanine-nucleotide-exchange factor (GEF) P-Rex1 is engaged downstream of GPCRs and phosphoinositide 3-kinase (PI3K) in many cell types, and promotes tumorigenic signalling and metastasis in breast cancer and melanoma, respectively. Although P-Rex1-dependent functions have been attributed to its GEF activity towards Rac1, we show that P-Rex1 also acts as a GEF for the Rac-related GTPase RhoG, both in vitro and in GPCR-stimulated primary mouse neutrophils. Furthermore, loss of either P-Rex1 or RhoG caused equivalent reductions in GPCR-driven Rac activation and Rac-dependent NADPH oxidase activity, suggesting they both function upstream of Rac in this system. Loss of RhoG also impaired GPCR-driven recruitment of the Rac GEF DOCK2, and F-actin, to the leading edge of migrating neutrophils. Taken together, our results reveal a new signalling hierarchy in which P-Rex1, acting as a GEF for RhoG, regulates Rac-dependent functions indirectly through RhoG-dependent recruitment of DOCK2. These findings thus have broad implications for our understanding of GPCR signalling to Rho GTPases and the actin cytoskeleton

Precarious Economies: Capitalism’s Creative Destruction in the Age of Neoliberal Campus Planning

The Precarious Economies working group engaged the University of Nevada Reno’s (UNR) Campus Master Plan (CMP) from the perspective of precarity—broadly understood as material conditions of vulnerability that threaten living bodies and are outside of one’s control. Employing traditional and in situ methods of rhetorical analysis and fieldwork, we investigated how the creative destruction of Reno’s emerging technology economy implicates people within precarity frames through facets of daily living including labor, housing, and transportation. Our mixed approaches allowed us to search for the material impacts of capitalism’s development on the lives of Reno’s residents and see the CMP’s (re)distribution of precarity as a symptom of capitalism’s creative destruction. In this essay, we describe the methods of our research and reflect on what the hybrid research approach of the working group teaches us about UNR/Reno and the contemporary function of capitalism