Signaling initiated by the secretory compartment

Classical signal transduction is initiated at the plasma membrane by extracellular signals and propagates to the cytosolic face of the same membrane. Multiple studies have shown that endomembranes can act as signaling platforms for this plasma-membrane-originated signaling. Recent evidence has indicated that endomembranes can also trigger their own signaling cascades that involve some of the molecular players that are classically engaged in signal transduction at the plasma membrane. Endomembrane-initiated signaling is important for synchronization of the functioning of the secretory pathway and coordination of the activities of the secretory organelles with other cellular machineries. However, these endomembrane-initiated regulatory circuits are only partially understood to date. This novel field is slowed by a lack of specific tools and the objective difficulties in the study of signal transduction of endomembrane-localized receptors, as their accessibility is limited. For example, the ligand-binding site of the KDEL receptor (that transduces endomembrane signaling) is positioned in the lumen of the Golgi complex. Here we report some approaches that are suitable for the study of endomembrane-initiated signaling.