A5075529568- Cellular transport and secretion
- Developmental Biology and Gene Regulation
- Retinal Development and Disorders
- Neurobiology and Insect Physiology Research
- Ubiquitin and proteasome pathways
- Microtubule and mitosis dynamics
- Protein Tyrosine Phosphatases
- Hippo pathway signaling and YAP/TAZ
- Plant Molecular Biology Research
- Endoplasmic Reticulum Stress and Disease
- Cancer-related gene regulation
- Histone Deacetylase Inhibitors Research
- Insect Resistance and Genetics
- Signaling Pathways in Disease
- Congenital heart defects research
- Invertebrate Immune Response Mechanisms
- Pluripotent Stem Cells Research
- Wnt/β-catenin signaling in development and cancer
Heinrich Heine University Düsseldorf
2012-2025
Notch signalling plays a crucial role in many developmental, homoeostatic and pathological processes metazoans. The pathway is activated by binding of the ligand to receptor, which changes conformation receptor exerting pulling force. force generated endocytosis interacting into signal-sending cell. Endocytosis ligands requires action E3 ligases Mindbomb1 (Mib1) Neuralized (Neur) that ubiquitylate lysines (Ks) their intracellular domains. It has been shown human MIB1 binds JAGGED1 (JAG1) via...
Summary The tumour suppressor Lethal (2) giant discs (Lgd) is a regulator of endosomal trafficking the Notch signalling receptor as well other transmembrane proteins in Drosophila. loss its function results an uncontrolled ligand-independent activation receptor. Here, we investigated consequences lgd and requirements for Notch. We show that cells independent Kuz dependent on γ-secretase. found have defect delays degradation proteins, which are residents plasma membrane. Furthermore, our...
The small GTPases Rab5 and Rab7 are important organisers of endosome formation maturation. In addition they orchestrate the trafficking cargo through endosomal pathway. A crucial event during maturation endosomes is replacement early organiser with late in a process called Rab conversion. conversion prerequisite for events, chief among them fusion matured lysosome. Recent work identifies members Sand1/Mon1 protein family as critical factors this process. Here, we present analysis function...
The bristle sensillum of the imago Drosophila is made four cells that arise from a sensory organ precursor cell (SOP). This SOP selected within proneural clusters (PNC) through mechanism involves Notch signalling. PNCs are defined expression domains genes, whose activities enables to become SOPs. They encode tissue specific bHLH proteins form functional heterodimers with protein Daughterless (Da). In prevailing lateral inhibition model for selection, transcriptional feedback loop pathway...
Recent work indicates that defects in late phases of the endosomal pathway caused by loss function tumour suppressor gene lethal (2) giant discs (lgd) or ESCRT complexes I-III result ligand-independent activation Notch all imaginal disc cells Drosophila melanogaster. lgd encodes a member an uncharacterised protein family, whose members contain one C2 domain and four repeats DM14 domain. The is unknown. We here report detailed structure-function analysis Lgd protein, which reveals domains are...
The emergence of the sensory organ precursor (SOP) from an equivalence group in Drosophila is a paradigm for studying single-cell fate specification through Notch-mediated lateral inhibition. Yet, it remains unclear how only single SOP selected relatively large cells. We show here that critical aspect selection controlled by cis-inhibition (CI), whereby Notch ligands, Delta (Dl), cis-inhibit receptors same cell. Based on observation mammalian ligand Dl-like 1 cannot , we probe role CI vivo....
Ubiquitylation (ubi) by the E3-ligases Mindbomb1 (Mib1) and Neuralized (Neur) is required for activation of DSL ligands Delta (Dl) Serrate (Ser) to activate Notch signalling. These ligases transfer ubiquitin lysines ligands' intracellular domains (ICDs), which sends them into an Epsin-dependent endocytic pathway. Here, we have tested requirement ubi Dl We found that requires its full function, but can also signal in two ubi-independent modes, one dependent independent Neur. identified neural...
Abstract Background Ubiquitylation (ubi) of the intracellular domain Notch ligand Delta (Dl) by E3 ligases Neuralized (Neur) and Mindbomb1 (Mib1) on lysines (Ks) is thought to be essential for its signalling activity. Nevertheless, we have previously shown that DlK2R-HA, a Dl variant where all Ks in (ICD) are replaced structurally similar arginine (R), still possess weak activity if over-expressed. This suggests ubi not absolutely required signalling. However, it known whether residual...
Wing development in Drosophila requires the activation of Wingless (Wg) a small stripe along boundary Fringe (Fng) expressing and non-expressing cells (FB), which coincides with dorso-ventral (D/V) wing imaginal disc. The expression Wg is induced by interactions between dorsal ventral mediated Notch signalling pathway. It appears that mutual from to ligands Serrate (Ser) Delta (Dl) respectively establishes symmetric domain straddles D/V boundary. directional these modification...
Members of the LGD/CC2D1 protein family contain repeats family-defining DM14 domains. Via this domain, they interact with members CHMP family, which are essential for ESCRT machinery-mediated formation intraluminal vesicles during endosome maturation. Here, we investigate requirement domains function Lgd in detail. We found that although both odd-numbered DM14s can act a functionally redundant manner, redundancy is not complete and contribute to full Lgd. Our analysis indicates some AAs form...
Abstract The emergence of the sensory organ precursor (SOP) from proneural equivalence group in Drosophila melanogaster is a paradigm for studying single cell fate specification through process lateral inhibition. Classical inhibition models describing this selection are based on transcriptional feedback mechanism where inhibitory signals between neighbouring cells, mediated by Notch pathway, coupled to an intracellular circuit regulating expression ligand Delta (Dl). It was previously shown...