Figure 2.

Proposed model of Gcgr trafficking and signaling. Stimulations with glucagon induce glucagon receptor recruitment into clathrin-coated vesicles on the plasma membrane through the interaction of β-arrestins with the cytoplasmic tail of the receptor and subsequent interaction with the clathrin coat. Short-term stimulations with glucagon increase glucagon receptor presence in early endosomes and enhanced signaling, followed by receptor recycling. Upon long-term treatments, reoccurrence of the receptor on the membrane is reduced, and its lysosomal degradation increases. Regulators of these sorting mechanisms on early and late endosomes, such as retromer and WASH complex for recycling and ESCRTs for degradation have been shown to be involved in other GPCR trafficking, however, the knowledge on Gcgr is still very limited and represented by question marks.