title: Cysteine-rich region of X-Serrate-1 is required for activation of Notch signaling in Xenopus primary neurogenesis.
abstract: The Notch family genes encode single-pass transmembrane proteins which function in a variety of cell fate specifications in invertebrates and vertebrates. In Xenopus primary neurogenesis, the Notch ligands, X-Delta-1 and X-Serrate-1, mediate Notch signaling and regulate cell differentiation. In the present study, we examined the role of the Serrate-specific cysteine-rich (CR) region in the primary neurogenesis of Xenopus embryos. The ligand constructs containing the DSL (Delta/Serrate/Lag-2) domain in the extracellular region caused a reduction in primary neurons, whereas the DSL-deleted form of X-Delta-1 resulted in the overproduction of primary neurons. However, the DSL-deleted form of X-Serrate-1 or the construct containing only the CR region in the extracellular domain (SerCR) reduced the number of primary neurons. In contrast, the CR-deleted form of X-Serrate-1 (SerACR) lost activity as a Notch ligand, regardless of the presence of the DSL domain within the extracellular domain. Overexpression of X-Delta-1 and X-Serrate-1 strongly induced the expression of Xenopus ESR-1 (XESR-1), a gene related to Drosophila Enhancer of split. SerCR alone also moderately induced the expression of XESR-1, but the SerACR form did not induce this expression. Co-injection of X-Notch-1deltaICD, which deletes the intracellular domain (ICD), with SerCR suppressed a neurogenic phenotype, although co-injection of X-Su(H)1DBM with SerCR did not, indicating that SerCR affects primary neurogenesis through the Notch/Su(H) pathway. These results suggestthatthe CR region of Xenopus Serrate is required for the activation of Notch signaling and cell fate specification in primary neurogenesis.
authors.affiliation: Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, Sanda, Hyogo, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Kiyota
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins; D003545:Cysteine / Q000737:chemistry*; D029721:Drosophila Proteins; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology*; D008957:Models, Genetic; D009474:Neurons / Q000166:cytology / Q000473:pathology; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction; D013696:Temperature; D014981:Xenopus; D029867:Xenopus Proteins
chemical_list: D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D008024:Ligands; D008565:Membrane Proteins; D012333:RNA, Messenger; D051880:Receptors, Notch; C000606278:Ser protein, Drosophila; D000072099:Serrate-Jagged Proteins; D029867:Xenopus Proteins; C000606280:jag1 protein, Xenopus; D003545:Cysteine