Biomaterial Database

The tumour suppressor Lethal (2) giant discs is required for the function of the ESCRT-III component Shrub/CHMP4. 2012

Tobias Troost, and Sandra Jaeckel, and Nadja Ohlenhard, and Thomas Klein

Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse1, 40225, Düsseldorf, Germany.

Recent work indicates that defects in late phases of the endosomal pathway caused by loss of function of the tumour suppressor gene lethal (2) giant discs (lgd) or the function of the ESCRT complexes I-III result in the ligand-independent activation of the Notch pathway in all imaginal disc cells in Drosophila melanogaster. lgd encodes a member of an uncharacterised protein family, whose members contain one C2 domain and four repeats of the DM14 domain. The function of the DM14 domain is unknown. We here report a detailed structure-function analysis of Lgd protein, which reveals that the DM14 domains are essential for the function of Lgd and act in a redundant manner. Moreover, our analysis indicates that the DM14 domain provides the specific function, whereas the C2 domain is required for the subcellular location of Lgd. We found that Lgd interacts directly with the ESCRT-III subunit Shrub through the DM14 domains. The interaction is required for the function of Shrub, indicating that Lgd contributes to the function of the ESCRT-III complex. Furthermore, our genetic studies indicate that the activation of Notch in ESCRT and lgd mutant cells occurs in a different manner and that the activity of Shrub and other ESCRT components are required for the activation of Notch in lgd mutant cells.

UI	MeSH Term	Description	Entries
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D009419	Nerve Tissue Proteins		Proteins, Nerve Tissue,Tissue Proteins, Nerve
D003600	Cytosol	Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.	Cytosols
D004331	Drosophila melanogaster	A species of fruit fly frequently used in genetics because of the large size of its chromosomes.	D. melanogaster,Drosophila melanogasters,melanogaster, Drosophila
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017344	Genes, Insect	The functional hereditary units of INSECTS.	Insect Genes,Gene, Insect,Insect Gene
D051880	Receptors, Notch	A family of conserved cell surface receptors that contain EPIDERMAL GROWTH FACTOR repeats in their extracellular domain and ANKYRIN REPEATS in their cytoplasmic domains. The cytoplasmic domains are released upon ligand binding and translocate to the CELL NUCLEUS, where they act as transcription factors.	Notch Protein,Notch Receptor,Notch Receptors,Notch Proteins,Protein, Notch,Receptor, Notch
D054730	Protein Interaction Domains and Motifs	Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.	Protein Interaction Domains,Protein Interaction Motifs,Binding Motifs, Protein Interaction,Protein Interaction Binding Motifs,Protein-Protein Interaction Domains,Domain, Protein Interaction,Domain, Protein-Protein Interaction,Domains, Protein Interaction,Domains, Protein-Protein Interaction,Motif, Protein Interaction,Motifs, Protein Interaction,Protein Interaction Domain,Protein Interaction Motif,Protein Protein Interaction Domains,Protein-Protein Interaction Domain
D056827	Endosomal Sorting Complexes Required for Transport	A set of protein subcomplexes involved in PROTEIN SORTING of UBIQUITINATED PROTEINS into intraluminal vesicles of MULTIVESICULAR BODIES and in membrane scission during formation of intraluminal vesicles, during the final step of CYTOKINESIS, and during the budding of enveloped viruses. The ESCRT machinery is comprised of the protein products of Class E vacuolar protein sorting genes.	ESCRT Complexes,ESCRT I,ESCRT II,ESCRT III,ESCRT Machinery,Endosomal Sorting Complex Required for Transport,Endosomal Sorting Complex Required for Transport I,Endosomal Sorting Complex Required for Transport II,Endosomal Sorting Complex Required for Transport III,Endosomal Sorting Complex Required for Transport Machinery,Complexes, ESCRT,Machinery, ESCRT
D060227	Imaginal Discs	Hollow sacs of cells in LARVA that form adult structures in insects during BIOLOGICAL METAMORPHOSIS.	Imaginal Disks,Disc, Imaginal,Discs, Imaginal,Disk, Imaginal,Disks, Imaginal,Imaginal Disc,Imaginal Disk