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How to take autophagy and endocytosis up a notch.

Barth JM, Köhler K - Biomed Res Int (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland ; Department of Biosciences, Centre for Ecological and Evolutionary Synthesis, University of Oslo, 0316 Oslo, Norway.

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.

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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.
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fig1: 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.

Mentions: Autophagy can be activated by a wide range of signals but most intersect at the central regulator of autophagy and the target of rapamycin (TOR) complex 1 (TORC1, see Figure 1(a)). TORC1 inhibits autophagy by phosphorylating the core autophagy proteins associated into the Atg1 (autophagy-related gene 1) complex. Upon autophagy induction, this inhibition is released, and the activation of the Atg1 complex is followed by the assembly of proteins and lipids at the sites of autophagosome formation. This vesicle nucleation requires the activation of a class III PI3K (phosphoinositide 3-kinase) complex containing Vps34 (vacuolar protein sorting 34), Vps15, and Atg6/Beclin. Once initiated, the expansion and closure of the autophagic vesicle is mediated by two ubiquitin-like systems, Atg5-Atg12 and Atg8 (see Figure 1(b)). After completion, the autophagosome can fuse with compartments of the endocytic pathway, such as early endosomes, multivesicular bodies (MVBs), or late endosomes prior to fusion with lysosomes. Eventually, the autophagosomal cargo gets degraded by the acidic hydrolases of the lysosome and essential molecules such as amino acids are recycled and reused for cellular processes (for review, see [4–7]).


How to take autophagy and endocytosis up a notch.

Barth JM, Köhler K - Biomed Res Int (2014)

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.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4016896&req=5

fig1: 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.
Mentions: Autophagy can be activated by a wide range of signals but most intersect at the central regulator of autophagy and the target of rapamycin (TOR) complex 1 (TORC1, see Figure 1(a)). TORC1 inhibits autophagy by phosphorylating the core autophagy proteins associated into the Atg1 (autophagy-related gene 1) complex. Upon autophagy induction, this inhibition is released, and the activation of the Atg1 complex is followed by the assembly of proteins and lipids at the sites of autophagosome formation. This vesicle nucleation requires the activation of a class III PI3K (phosphoinositide 3-kinase) complex containing Vps34 (vacuolar protein sorting 34), Vps15, and Atg6/Beclin. Once initiated, the expansion and closure of the autophagic vesicle is mediated by two ubiquitin-like systems, Atg5-Atg12 and Atg8 (see Figure 1(b)). After completion, the autophagosome can fuse with compartments of the endocytic pathway, such as early endosomes, multivesicular bodies (MVBs), or late endosomes prior to fusion with lysosomes. Eventually, the autophagosomal cargo gets degraded by the acidic hydrolases of the lysosome and essential molecules such as amino acids are recycled and reused for cellular processes (for review, see [4–7]).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Biology, Institute of Molecular Systems Biology, ETH Zürich, 8093 Zürich, Switzerland ; Department of Biosciences, Centre for Ecological and Evolutionary Synthesis, University of Oslo, 0316 Oslo, Norway.

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.

Show MeSH
Related in: MedlinePlus