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The correct establishment and maintenance of unidirectional Notch signaling are critical for the homeostasis of various stem cell lineages. However, the molecular mechanisms that prevent cell-autonomous ectopic Notch signaling activation and deleterious cell fate decisions remain unclear. Here we show that the retromer complex directly and specifically regulates Notch receptor retrograde trafficking in Drosophila neuroblast lineages to ensure the unidirectional Notch signaling from neural progenitors to neuroblasts. Notch polyubiquitination mediated by E3 ubiquitin ligase Itch/Su(dx) is inherently inefficient within neural progenitors, relying on retromer-mediated trafficking to avoid aberrant endosomal accumulation of Notch and cell-autonomous signaling activation. Upon retromer dysfunction, hypo-ubiquitinated Notch accumulates in Rab7+ enlarged endosomes, where it is ectopically processed and activated in a ligand-dependent manner, causing progenitor-originated tumorigenesis. Our results therefore unveil a safeguard mechanism whereby retromer retrieves potentially harmful Notch receptors in a timely manner to prevent aberrant Notch activation-induced neural progenitor dedifferentiation and brain tumor formation.
Pubmed ID: 30176986 RIS Download
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View all literature mentionsGlobal nonprofit biological resource center (BRC) and research organization that provides biological products, technical services and educational programs to private industry, government and academic organizations. Its mission is to acquire, authenticate, preserve, develop and distribute biological materials, information, technology, intellectual property and standards for the advancement and application of scientific knowledge. The primary purpose of ATCC is to use its resources and experience as a BRC to become the world leader in standard biological reference materials management, intellectual property resource management and translational research as applied to biomaterial development, standardization and certification. ATCC characterizes cell lines, bacteria, viruses, fungi and protozoa, as well as develops and evaluates assays and techniques for validating research resources and preserving and distributing biological materials to the public and private sector research communities.
View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsAmerican chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.
View all literature mentionsAn antibody supplier which banks and distributes hybridomas and monoclonal antibodies for use in research. The bank includes antibodies against targets such as GFP, transcription factors, stem cells, and human.
View all literature mentionsServes Drosophila research community by collecting and distributing DNA clones and vectors; collecting and distributing Drosophila cell lines; developing and testing genomics technologies for use in Drosophila and assisting members of the research community in their use.
View all literature mentionsCell line HEK293 is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDrosophila melanogaster with name w[1118] from BDSC.
View all literature mentionsThis monoclonal targets Notch, intracellular domain
View all literature mentionsThis monoclonal targets Delta, extracellular domain
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets Patched (extracellular region)
View all literature mentionsThis monoclonal targets Myc-Tag
View all literature mentionsThis polyclonal targets V5 Tag
View all literature mentionsThis monoclonal targets Mouse Drosophila Wingless protein
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis polyclonal targets PRKCA, PRKCG, PRKCB
View all literature mentionsThis monoclonal targets Notch, extracellular domain, EGF repeats #12-20
View all literature mentionsThis monoclonal targets beta-galactosidase
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets V5 Agarose Affinity Gel antibody produced in mouse
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00841}attP2 from BDSC.
View all literature mentionsThis monoclonal targets Notch, intracellular domain
View all literature mentionsThis monoclonal targets Delta, extracellular domain
View all literature mentionsThis polyclonal targets V5 Tag
View all literature mentionsThis polyclonal targets FLAG
View all literature mentionsThis monoclonal targets Patched (extracellular region)
View all literature mentionsThis monoclonal targets Mouse Drosophila Wingless protein
View all literature mentionsThis polyclonal targets PRKCA, PRKCG, PRKCB
View all literature mentionsThis monoclonal targets Prospero protein
View all literature mentionsThis monoclonal targets Notch, extracellular domain, EGF repeats #12-20
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-FLP.Exel}3, P{w[+mC]=Ubi-p63E(FRT.STOP)Stinger}15F2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab11.S25N}35 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab9.S26N}04 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UASp-YFP.Rab9.Q71L}20 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab9}22 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rab7.Q67L}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab7.T22N}06 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rab5.S43N}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UASp-YFP.Rab5.Q88L}01a/TM3, Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab5}02 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=sqh-EYFP-Golgi}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-mito-HA-GFP.AP}2/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-GFP-LAMP}2; P{w[+m*]=nSyb-GAL4.S}3/T(2;3)TSTL, CyO: TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.JF02218}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-Egfr.DN.B}29-77-1; P{w[+mC]=UAS-Egfr.DN.B}29-8-1 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-kuz.DN}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-Psn.527.D447A}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Dl.DN}TJ3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Su(dx).C}IIa from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00045}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00840}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-ptc.1130X.YFP}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00794}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01309}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01769}attP40 from BDSC.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UAS-mito-HA-GFP.AP}2/CyO from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-GFP-LAMP}2; P{w[+m*]=nSyb-GAL4.S}3/T(2;3)TSTL, CyO: TM6B, Tb[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UAS-Egfr.DN.B}29-77-1; P{w[+mC]=UAS-Egfr.DN.B}29-8-1 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-kuz.DN}2 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Rab5.S43N}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[1118]; P{w[+mC]=UASp-YFP.Rab5.Q88L}01a/TM3, Ser[1] from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab5}02 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=sqh-EYFP-Golgi}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[1118]; P{w[+mC]=UAS-Psn.527.D447A}3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Dl.DN}TJ3 from BDSC.
View all literature mentionsDrosophila melanogaster with name w[*]; P{w[+mC]=UAS-Su(dx).C}IIa from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00840}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS00794}attP2 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] v[1]; P{y[+t7.7] v[+t1.8]=TRiP.HMS01769}attP40 from BDSC.
View all literature mentionsDrosophila melanogaster with name y[1] w[*]; P{w[+mC]=UASp-YFP.Rab9}22 from BDSC.
View all literature mentionsThis unknown targets ANTI-FLAG(R) M2 Affinity Gel
View all literature mentionsThis monoclonal targets V5 Agarose Affinity Gel antibody produced in mouse
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