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Cells Feb 2024Cell death plays an essential function in organismal development, wellbeing, and ageing. Many types of cell deaths have been described in the past 30 years. Among these,... (Review)
Review
Cell death plays an essential function in organismal development, wellbeing, and ageing. Many types of cell deaths have been described in the past 30 years. Among these, apoptosis remains the most conserved type of cell death in metazoans and the most common mechanism for deleting unwanted cells. Other types of cell deaths that often play roles in specific contexts or upon pathological insults can be classed under variant forms of cell death and programmed necrosis. Studies in have contributed significantly to the understanding and regulation of apoptosis pathways. In addition to this, has also served as an essential model to study the genetic basis of autophagy-dependent cell death (ADCD) and other relatively rare types of context-dependent cell deaths. Here, we summarise what is known about apoptosis, ADCD, and other context-specific variant cell death pathways in , with a focus on developmental cell death.
Topics: Animals; Drosophila; Cell Death; Apoptosis; Drosophila Proteins; Autophagic Cell Death
PubMed: 38391960
DOI: 10.3390/cells13040347 -
Drosophila CLASP regulates microtubule orientation and dendrite pruning by suppressing Par-1 kinase.Cell Reports May 2022The evolutionarily conserved CLASPs (cytoplasmic linker-associated proteins) are microtubule-associated proteins that inhibit microtubule catastrophe and promote rescue....
The evolutionarily conserved CLASPs (cytoplasmic linker-associated proteins) are microtubule-associated proteins that inhibit microtubule catastrophe and promote rescue. CLASPs can regulate axonal elongation and dendrite branching in growing neurons. However, their roles in microtubule orientation and neurite pruning in remodeling neurons remain unknown. Here, we identify the Drosophila CLASP homolog Orbit/MAST, which is required for dendrite pruning in ddaC sensory neurons during metamorphosis. Orbit is important for maintenance of the minus-end-out microtubule orientation in ddaC dendrites. Our structural analysis reveals that the microtubule lattice-binding TOG2 domain is required for Orbit to regulate dendritic microtubule orientation and dendrite pruning. In a genetic modifier screen, we further identify the conserved Par-1 kinase as a suppressor of Orbit in dendritic microtubule orientation. Moreover, elevated Par-1 function impairs dendritic microtubule orientation and dendrite pruning, phenocopying orbit mutants. Overall, our study demonstrates that Drosophila CLASP governs dendritic microtubule orientation and dendrite pruning at least partly via suppressing Par-1 kinase.
Topics: Animals; Drosophila; Drosophila Proteins; Glycogen Synthase Kinase 3; Metamorphosis, Biological; Microtubules; Neuronal Plasticity
PubMed: 35649352
DOI: 10.1016/j.celrep.2022.110887 -
Current Biology : CB Apr 20247An efficient immune system must provide protection against a broad range of pathogens without causing excessive collateral tissue damage. While immune effectors have...
7An efficient immune system must provide protection against a broad range of pathogens without causing excessive collateral tissue damage. While immune effectors have been well characterized, we know less about the resilience mechanisms protecting the host from its own immune response. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes. While protective against pathogens, AMPs can be cytotoxic to host cells. Here, we reveal that a family of stress-induced proteins, the Turandots, protect the Drosophila respiratory system from AMPs, increasing resilience to stress. Flies lacking Turandot genes are susceptible to environmental stresses due to AMP-induced tracheal apoptosis. Turandot proteins bind to host cell membranes and mask negatively charged phospholipids, protecting them from cationic pore-forming AMPs. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy.
Topics: Animals; Drosophila; Antimicrobial Peptides; Antimicrobial Cationic Peptides; Immunity, Innate; Drosophila Proteins
PubMed: 38484734
DOI: 10.1016/j.cub.2024.02.049 -
Fly Dec 2022MicroRNAs (miRNAs) are a class of small non-coding RNAs ~19-22 nt long which post-transcriptionally regulate gene expression. Their ability to exhibit dynamic expression... (Review)
Review
MicroRNAs (miRNAs) are a class of small non-coding RNAs ~19-22 nt long which post-transcriptionally regulate gene expression. Their ability to exhibit dynamic expression patterns coupled with their wide variety of targets allows miRNAs to regulate many processes, including the innate immune response of . Recent studies have identified miRNAs in which are differentially expressed during infection with different pathogens as well as miRNAs that may affect immune signalling when differentially expressed. This review provides an overview of miRNAswhich have been identified to play a role in the immune response of through targeting of the Toll and IMD signalling pathways and other immune processes. It will also explore the role of miRNAs in fine-tuning the immune response in and highlight current gaps in knowledge regarding the role of miRNAs in immunity and areas for further research.
Topics: Animals; Drosophila; MicroRNAs; Drosophila melanogaster; Immunity, Innate; Drosophila Proteins
PubMed: 36412256
DOI: 10.1080/19336934.2022.2149204 -
Molecules and Cells Dec 2020The genome contains four low molecular weightprotein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical...
The genome contains four low molecular weightprotein tyrosine phosphatase (LMW-PTP) members: Primo-1, Primo-2, CG14297, and CG31469. The lack of intensive biochemical analysis has limited our understanding of these proteins. Primo-1 and CG31469 were previously classified as pseudophosphatases, but CG31469 was also suggested to be a putative protein arginine phosphatase. Herein, we present the crystal structures of CG31469 and Primo-1, which are the first LMW-PTP structures. Structural analysis showed that the two proteins adopt the typical LMW-PTP fold and have a canonically arranged P-loop. Intriguingly, while Primo-1 is presumed to be a canonical LMW-PTP, CG31469 is unique as it contains a threonine residue at the fifth position of the P-loop motif instead of highly conserved isoleucine and a characteristically narrow active site pocket, which should facilitate the accommodation of phosphoarginine. Subsequent biochemical analysis revealed that Primo-1 and CG31469 are enzymatically active on phosphotyrosine and phosphoarginine, respectively, refuting their classification as pseudophosphatases. Collectively, we provide structural and biochemical data on two proteins: Primo-1, the canonical LMW-PTP protein, and CG31469, the first investigated eukaryotic protein arginine phosphatase. We named CG31469 as DARP, which stands for ARginine Phosphatase.
Topics: Amino Acid Sequence; Animals; Catalytic Domain; Drosophila Proteins; Drosophila melanogaster; Molecular Weight; Protein Tyrosine Phosphatases; Structure-Activity Relationship
PubMed: 33372666
DOI: 10.14348/molcells.2020.0192 -
Biology Open Jul 2022The compartmentalized domains of polarized epithelial cells arise from mutually antagonistic actions between the apical Par complex and the basolateral Scrib module. In...
The compartmentalized domains of polarized epithelial cells arise from mutually antagonistic actions between the apical Par complex and the basolateral Scrib module. In Drosophila, the Scrib module proteins Scribble (Scrib) and Discs-large (Dlg) are required to limit Lgl phosphorylation at the basolateral cortex, but how Scrib and Dlg could carry out such a 'protection' activity is not clear. We tested Protein Phosphatase 1α (PP1) as a potential mediator of this activity, but demonstrate that a significant component of Scrib and Dlg regulation of Lgl is PP1 independent, and found no evidence for a Scrib-Dlg-PP1 protein complex. However, the Dlg SH3 domain plays a role in Lgl protection and, in combination with the N-terminal region of the Dlg HOOK domain, in recruitment of Scrib to the membrane. We identify a 'minimal Dlg' comprised of the SH3 and HOOK domains that is both necessary and sufficient for Scrib localization and epithelial polarity function in vivo. This article has an associated First Person interview with the first author of the paper.
Topics: Animals; Drosophila; Drosophila Proteins; Epithelial Cells; Humans
PubMed: 35722710
DOI: 10.1242/bio.059408 -
Cell Death and Differentiation Jan 2022The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place...
The Drosophila IAP protein, Diap2, is a key mediator of NF-κB signalling and innate immune responses. Diap2 is required for both local immune activation, taking place in the epithelial cells of the gut and trachea, and for mounting systemic immune responses in the cells of the fat body. We have found that transgenic expression of Diap2 leads to a spontaneous induction of NF-κB target genes, inducing chronic inflammation in the Drosophila midgut, but not in the fat body. Drice is a Drosophila effector caspase known to interact and form a stable complex with Diap2. We have found that this complex formation induces its subsequent degradation, thereby regulating the amount of Diap2 driving NF-κB signalling in the intestine. Concordantly, loss of Drice activity leads to accumulation of Diap2 and to chronic intestinal inflammation. Interestingly, Drice does not interfere with pathogen-induced signalling, suggesting that it protects from immune responses induced by resident microbes. Accordingly, no inflammation was detected in transgenic Diap2 flies and Drice-mutant flies reared in axenic conditions. Hence, we show that Drice, by restraining Diap2, halts unwanted inflammatory signalling in the intestine.
Topics: Animals; Drosophila; Drosophila Proteins; Immunity, Innate; Inflammation; Inhibitor of Apoptosis Proteins; Signal Transduction
PubMed: 34262145
DOI: 10.1038/s41418-021-00832-w -
Cell Stress & Chaperones Jan 2021The small heat shock proteins (sHsps) are a ubiquitous family of ATP-independent stress proteins found in all domains of life. Drosophila melanogaster Hsp27 (DmHsp27) is...
The small heat shock proteins (sHsps) are a ubiquitous family of ATP-independent stress proteins found in all domains of life. Drosophila melanogaster Hsp27 (DmHsp27) is the only known nuclear sHsp in insect. Here analyzing sequences from HMMER, we identified 56 additional insect sHsps with conserved arginine-rich nuclear localization signal (NLS) in the N-terminal region. At this time, the exact role of nuclear sHsps remains unknown. DmHsp27 protein-protein interaction analysis from iRefIndex database suggests that this protein, in addition to a putative role of molecular chaperone, is likely involved in other nuclear processes (i.e., chromatin remodeling and transcription). Identification of DmHsp27 interactors should provide key insights on the cellular and molecular functions of this nuclear chaperone.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Heat-Shock Proteins, Small; Insect Proteins; Insecta; Protein Interaction Maps
PubMed: 32888179
DOI: 10.1007/s12192-020-01156-3 -
Neuron Mar 2022The nervous and endocrine systems coordinately monitor and regulate nutrient availability to maintain energy homeostasis. Sensory detection of food regulates internal...
The nervous and endocrine systems coordinately monitor and regulate nutrient availability to maintain energy homeostasis. Sensory detection of food regulates internal nutrient availability in a manner that anticipates food intake, but sensory pathways that promote anticipatory physiological changes remain unclear. Here, we identify serotonergic (5-HT) neurons as critical mediators that transform gustatory detection by sensory neurons into the activation of insulin-producing cells and enteric neurons in Drosophila. One class of 5-HT neurons responds to gustatory detection of sugars, excites insulin-producing cells, and limits consumption, suggesting that they anticipate increased nutrient levels and prevent overconsumption. A second class of 5-HT neurons responds to gustatory detection of bitter compounds and activates enteric neurons to promote gastric motility, likely to stimulate digestion and increase circulating nutrients upon food rejection. These studies demonstrate that 5-HT neurons relay acute gustatory detection to divergent pathways for longer-term stabilization of circulating nutrients.
Topics: Animals; Drosophila Proteins; Drosophila melanogaster; Nutrients; Serotonergic Neurons; Taste
PubMed: 35051377
DOI: 10.1016/j.neuron.2021.12.028 -
Developmental Cell Nov 2019Homologous chromosomes pair in somatic cells in Drosophila, but how this occurs is poorly understood. In this issue of Developmental Cell, Viets et al. (2019) show that...
Homologous chromosomes pair in somatic cells in Drosophila, but how this occurs is poorly understood. In this issue of Developmental Cell, Viets et al. (2019) show that proteins and chromatin structure mediate pairing and argue against a DNA sequence-based mechanism.
Topics: Animals; Cell Cycle; Chromosome Pairing; Drosophila; Drosophila Proteins; Drosophila melanogaster
PubMed: 31689384
DOI: 10.1016/j.devcel.2019.10.014