Abstract：
:Regulation of Notch signaling is critical to development and maintenance of most eukaryotic organisms. The Notch receptors and ligands are integral membrane proteins and direct cell-cell interactions are needed to activate signaling. Ligand-expressing cells activate Notch signaling through an unusual mechanism involving Notch proteolysis to release the intracellular domain from the membrane, allowing the Notch receptor to function directly as the downstream signal transducer. In the absence of ligand, the Notch receptor is maintained in an autoinhibited, protease resistant state. Genetic studies suggest that Notch ligands require ubiquitylation, epsin endocytic adaptors and dynamin-dependent endocytosis for signaling activity. Here we discuss potential models and supporting evidence to account for the absolute requirement for ligand endocytosis to activate signaling in Notch cells. Specifically, we focus on a role for ligand-mediated endocytic force to unfold Notch, override the autoinhibited state, and activate proteolysis to direct Notch-specific cellular responses.
journal_name
Semin Cell Dev Bioljournal_title
Seminars in cell & developmental biologyauthors
Musse AA,Meloty-Kapella L,Weinmaster Gdoi
10.1016/j.semcdb.2012.01.011subject
Has Abstractpub_date
2012-06-01 00:00:00pages
429-36issue
4eissn
1084-9521issn
1096-3634pii
S1084-9521(12)00015-8journal_volume
23pub_type
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