How to take autophagy and endocytosis up a notch

Abstract

The interconnection of the endocytic and autophagosomal trafficking routes has been recognized more than two decades ago with both pathways using a set of identical effector proteins and sharing the same ultimate lysosomal destination. More recent data sheds light onto how other pathways are intertwined into this network, and how degradation via the endosomal/autophagosomal system may affect signaling pathways in multicellular organisms. Here, we briefly review the common features of autophagy and endocytosis and discuss how other players enter this mix with particular respect to the Notch signaling pathway.

Figure 1

Network of the Insulin/TOR, autophagy, endocytosis, and Notch pathways. The Insulin/TOR pathway (a) normally inhibits the autophagic machinery (b). Notch signaling is induced by ligand (DSL) binding to the receptor and the cleaved NICD activates target gene expression (c). Alternatively, Notch can be activated ligand independently through receptor endocytosis ((d)2)), or the endocytosed receptor can be degraded to silence the signal ((d)1)). Connections of the pathways are shown between molecules directly or between molecules and the pathway in general (shaded areas). Bar-headed arrows indicate inhibition, arrows indicate activation. For simplicity, the trafficking routes are reduced to the processes and players discussed in the text. Numbers [] refer to publications cited in the text. Dark filled circles indicate drugs, whereas proteins are represented with white circles. RTK: receptor tyrosine kinase, RESV: resveratrol.