Role of conserved intracellular motifs in Serrate signalling, cis-inhibition and endocytosis
Date
2006Source
EMBO JournalVolume
25Pages
4697-4706Google Scholar check
Keyword(s):
Metadata
Show full item recordAbstract
Notch is the receptor in a signalling pathway that operates in a diverse spectrum of developmental processes. Its ligands (e.g. Serrate) are transmembrane proteins whose signalling competence is regulated by the endocytosis-promoting E3 ubiquitin ligases, Mindbomb1 and Neuralized. The ligands also inhibit Notch present in the same cell (cis-inhibition). Here, we identify two conserved motifs in the intracellular domain of Serrate that are required for efficient endocytosis. The first, a dileucine motif, is dispensable for trans-activation and cis-inhibition despite the endocytic defect, demonstrating that signalling can be separated from bulk endocytosis. The second, a novel motif, is necessary for interactions with Mindbomb1/Neuralized and is strictly required for Serrate to trans-activate and internalise efficiently but not for it to inhibit Notch signalling. Cis-inhibition is compromised when an ER retention signal is added to Serrate, or when the levels of Neuralized are increased, and together these data indicate that cis-inhibitory interactions occur at the cell surface. The balance of ubiquitinated/unubiquitinated ligand will thus affect the signalling capacity of the cell at several levels. © 2006 European Molecular Biology Organization | All Rights Reserved.
Collections
Cite as
Related items
Showing items related by title, author, creator and subject.
-
Article
Addressing the Functional Determinants of FAK during Ciliogenesis in Multiciliated Cells
Antoniades, Ioanna; Stylianou, Panayiota; Christodoulou, Neophytos; Skourides, Paris A. (2017)We previously identified focal adhesion kinase (FAK) as an important regulator of ciliogenesis in multiciliated cells. FAK and other focal adhesion (FA) proteins associate with the basal bodies and their striated rootlets ...
-
Article
Split-Inteins for Simultaneous, site-specific conjugation of Quantum Dots to multiple protein targets In vivo
Charalambous, Anna; Antoniades, Ioanna; Christodoulou, Neophytos; Skourides, Paris A. (2011)Background: Proteins labelled with Quantum Dots (QDs) can be imaged over long periods of time with ultrahigh spatial and temporal resolution, yielding important information on the spatiotemporal dynamics of proteins within ...
-
Article
Overexpression of the m4 and mα genes of the E(spl)-Complex antagonizes Notch mediated lateral inhibition
Apidianakis, Yiorgos; Nagel, A. C.; Chalkiadaki, Angeliki; Preiss, A.; Delidakis, Christos (1999)Intercellular signalling mediated by Notch proteins is crucial to many cell fate decisions in metazoans. Its profound effects on cell fate and proliferation require that a complex set of responses involving positive and ...