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First published online June 1, 2005

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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.

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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 Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Social Bookmarking                         What's this?