Figure 1. Study design and approach.

1. Schematic shows a system of two species of GTPases, mGTPases (mG), and heterotrimeric GTPases (tG), coupled by the linker protein, GIV/Girdin, that is localized on the Golgi membranes within the secretory pathway as the focus of this study. The circuit begins when active Arf1‐GTP directly binds GIV's N‐term HOOK domain, recruits GIV to Golgi membranes, and activates Gi (Lo et al, 2015; arrow 1). The circuit is completed when GIV's C‐terminus orchestrates two feedback loops (arrows 2 and 3), both of which are essential for the inactivation of Arf1 (Lo et al, 2015; Kalogriopoulos et al, 2019). See also Fig EV1 for illustrations detailing the sequential steps within the dynamic nature of the motif, and Movie EV1 for the visualization of these dynamic steps as a movie gif.
2. Schematic of the mathematical model that we used to study the role of such coupling of GTPase (top panel) in autocrine secretion‐supported cell survival and proliferation (bottom panel). The modeling in the top panel is experimentally constrained, and the modeling in the bottom panel is a predictive module. This model is based on the nominal time scale of these events (left panel) and has the typical behavior shown in the right panel.