FIGURE 1.

The secretory pathway is a signaling platform. The secretory pathway hosts several signaling machineries, whose function as autoregulatory systems has been characterized in detail. The ER localized AREX complex (1) and LTK-dependent system (2) are involved in regulating ER export of different proteins. Once proteins leave the ER, also ER resident chaperones reach the cis-Golgi, where they bind and activate the KDELR. Indeed, the KDELR activation stimulates both the Gs-PKA signaling (3) to regulate retrograde traffic and the Gq-SRC pathway (4) to promote the anterograde transport through the Golgi. Finally, proteins reach the TGN to be sorted and reach the final destination either inside or outside the cell. Specifically, basolateral proteins stimulate the GPRC5A receptor to activate PKD in order to exit the TGN (5).