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First published online June 1, 2005

Development 132, 1203e (2005)
© The Company of Biologists Limited
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In this issue

Activating Notch by ligand endocytosis

The Notch ligands – Delta/Serrate/Lag2 (DSL) – are transmembrane proteins that must be endocytosed in signal-sending cells to activate Notch on signal-receiving cells. Previous work has suggested that DSL signalling activity might be promoted by their mono-ubiquitination by the ubiquitin ligases Mind bomb (Mib) in zebrafish and Neuralized (Neur) in Drosophila, which possibly targets the ligands for Epsin-mediated endocytosis. Wang and Struhl now establish that, in Drosophila, DSL ligands must be ubiquitinated by Neur or Mib to undergo Epsin-mediated endocytosis, and must be endocytosed via Epsin activity to activate Notch (see p. 2883). They suggest that Epsin-mediated endocytosis has a special property that confers signalling activity to DSL ligands, perhaps by recruiting DSL proteins to certain cell surface micro-domains or by exerting a mechanical stress on the ligand-bound receptor. Alternatively, Epsin-mediated endocytosis might target DSL ligands to a specific recycling pathway for processing into active forms.



Related articles in Development:

Distinct roles for Mind bomb, Neuralized and Epsin in mediating DSL endocytosis and signaling in Drosophila
Weidong Wang and Gary Struhl
Development 2005 132: 2883-2894. [Abstract] [Full Text]  




This Article
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