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Review
, 19 (4), 323-8

Endocytic Regulation of Notch Signaling

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Review

Endocytic Regulation of Notch Signaling

Mark E Fortini et al. Curr Opin Genet Dev.

Abstract

Endocytosis and endosomal trafficking have emerged as important cell biological steps in the Notch developmental signaling pathway. Ligand endocytosis helps generate the physical forces needed to dissociate and activate the receptor, and activated receptors enter endosomes to signal productively. Endosomal trafficking is also responsible for downregulating Notch receptors that have not been activated by ligand. Recent studies have provided new insights into these Notch trafficking steps, and have uncovered additional endosomal mechanisms that contribute to asymmetric Notch activation and ligand-independent Notch signaling.

Figures

Figure 1
Figure 1
Overview of ligand and receptor endocytosis in the Notch signaling pathway. In the signal-sending cell (top), endocytosis of Notch ligands (violet) is needed for their productive signaling activity. Ligand endocytosis generates the physical forces needed to dissociate and activate Notch receptors in nascent invaginating endocytic vesicles, and it might also concentrate ligand molecules through their trafficking and/or post-translational modification in the recycling compartment. In the signal-receiving cell (bottom), Notch receptors (blue) are internalized into endocytic vesicles and subsequently routed to early endosomes. Ligand-activated Notch is sorted into multivesicular bodies and thence to lysosomes for degradation; non-ligand-activated Notch can undergo trafficking to the cell surface via recycling endosomes. The identities of various endocytic factors involved in these trafficking steps are shown near their approximate sites of activity; those that promote signaling are indicated in green whereas those involved in signaling down-regulation are indicated in red. The γ-secretase-mediated cleavage of Notch that generates the active signaling fragment NICD can occur at different points in the endosomal trafficking pathway (see text for details).

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