Chapter Fourteen - Biodiversity and Noncanonical Notch Signaling
Section snippets
A Wide Range of Notch-dependent Activities
Notch receptors trigger a wide range of cell fate choices through intercellular communications. Notch signaling is conserved across metazoan species and besides acquisition of specific cell fates and potentials enables also diverse cellular responses, like differentiation, proliferation, or apoptosis. Notch receptors function in multiple tissues and is used at various stages of development (Artavanis-Tsakonas et al., 1999, Kopan and Ilagan, 2009, Lai, 2004). Drosophila, where only a single
Noncanonical Notch Signaling and Bristle Patterning
In recent years, increasing examples of biological events have been reported that do not require the classical Delta-like DSL ligands nor the Su(H)-like CSL mediator. Some data reveal such a different pathway acting during Drosophila neurogenesis where multiple connections with the Wg signaling exist (Ramain et al., 2001, Hayward et al., 2008). The thorax of the flies exhibits two types of sensory organs, few large bristles, or macrochaetae, and numerous small bristles, or microchaetae. The
Noncanonical N Signals in Vertebrates
Increasing number of noncanonical Notch signals were observed and explored in mammals. In general, we define these as situations where signal transduction is possible independent of at least one component of the Notch core. These events include alternative ligands, alternative mediators, or proteolysis-independent Notch signals.
Misappropriation by Viruses
Some pathological virus infections can alienate CSL factors from their canonical function to serve the viruses’ own advantages. Viruses like the Epstein–Barr virus (EBV), Kaposi’s sarcoma-associated herpesvirus (KSHV), and adenovirus type 5 proteins are known to release multiple proteins necessary for cellular transformation that bind CSL and may modulate CSL-dependent transcription (Hsieh and Hayward, 1995). For example, the KSHV RTA factor and the EBV EBNA2 have antagonist consequence on B
New Insights on MAML
Recently, a noncanonical function of mam has been studied that enhances Hedgehog signaling specifically in stem cells of the Drosophila ovary (Vied and Kalderon, 2009). Rather than being a coactivator of Notch in these tissues, mam functions in follicle stem cells independently of Notch. There are increasing examples where mam-like transcriptional factors play unexpected roles in other signaling pathways including muscle differentiation and myopathies (MEF2C), tumor suppressor pathway (p53),
Rheostat and Fine-tuning
Nemo-like kinases (NLK) represent a family of conserved protein kinases that function in various tissues and biological events. Though Drosophila nemo was suspected to be involved in Notch signaling (Verheyen et al., 1996, Kankel et al., 2007), a very recent study in zebra fish established the NICD of Notch1 as a target and its phosphorylation contributes to decrease the formation of the CSL–MAML–NICD transcriptional complex (Ishitani et al., 2010). Knockdown Nlk leads to activation of HES
Nonnuclear Mechanisms
Finally, few reports described Notch signal transduction events that are independent from the cleavage.
Discussion
Notch mutants and most of the receptor transduction machinery were first identified in Drosophila. Due to partial redundancy among the Notch genes in vertebrates, the study of Notch receptors remains more sophisticated in Mouse or other mammalian models. Drosophila has only one receptor, and its powerful genetics continues to allow the identification of new modifiers that influence Notch signaling (Mummery-Widmer et al., 2009). Though the functional aspects of the different Notch domains has
Acknowledgments
I apologize to colleagues whose work was not cited. I am grateful to Inna Biryukova for artworks. This work was supported by the Association pour la Recherche sur le Cancer (ARC), the CNRS, the INSERM and the University of Strasbourg.
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