Small GTPase signaling and the unfolded protein response

The endoplasmic reticulum (ER), first compartment of the secretory pathway, is mainly involved in calcium sequestration and lipid biosynthesis and in the translation, folding, and transport of secretory proteins. Under some physiological and physiopathological situations, secretory proteins do not acquire their folded conformation and accumulate in the ER. An adaptive response named the UPR is then triggered from this compartment to restore its homeostasis. In the past few years, interconnections between the UPR and small GTPase signaling have been established. In an attempt to further investigate these novel signaling networks, we hereby provide a detailed description of experimental strategies available. We describe in detail methods to monitor both UPR and small GTPase signaling and the outcomes of such approaches in the identification of new links between those signaling pathways using pharmacological and genetic screens. In physiopathological contexts, the guidelines herein should enable researchers in the field to establish essential means for determination of functional interactions between those pathways.