The role of Peroxin 7 during Drosophila embryonic development

Genome ◽  
2020 ◽  
pp. 1-19
Author(s):  
C. Pridie ◽  
Andrew J. Simmonds
Keyword(s):  
Cell Lineage ◽  
Receptor Protein ◽  
Oxygen Species ◽  
Peroxisome Biogenesis ◽  
Tissue Specific ◽  
Over Expression ◽  
Cell Lineages ◽  
Targeting Signal ◽  
Cytosolic Receptor

Peroxisomes are organelles in eukaryotic cells responsible for processing several types of lipids and management of reactive oxygen species. A conserved family of peroxisome biogenesis (Peroxin, Pex) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 (PEX7) acts as a cytosolic receptor protein that targets enzymes containing a peroxisome targeting signal 2 (PTS2) motif for peroxisome matrix import. The PTS2 motif is not present in the Drosophila melanogaster homologs of these enzymes. However, the fly genome contains a Pex7 gene (CG6486) that is very similar to yeast and human PEX7. We find that Pex7 is expressed in tissue-specific patterns analogous to differentiating neuroblasts in D. melanogaster embryos. This is correlated with a requirement for Pex7 in this cell lineage as targeted somatic Pex7 knockout in embryonic neuroblasts reduced survival. We also found that Pex7 over-expression in the same cell lineages caused lethality during the larval stage. Targeted somatic over-expression of a Pex7 transgene in neuroblasts of Pex7 homozygous null mutants resulted in a semi-lethal phenotype similar to targeted Pex7 knockout. These findings suggest that D. melanogaster has tissue-specific requirements for Pex7 during embryo development.

scholarly journals Drosophila melanogaster Peroxisome Biogenesis Factor 7 plays a role in embryonic development

2019 ◽  
Author(s):  
C Pridie ◽  
AJ Simmonds
Keyword(s):  
Lipid Synthesis ◽  
Receptor Protein ◽  
Adult Survival ◽  
Peroxisome Biogenesis ◽  
Embryo Survival ◽  
Tissue Specific ◽  
Neural Precursors ◽  
Over Expression ◽  
The Central Nervous System ◽  
Embryo Stage

AbstractPeroxisomes are organelles responsible for aspects of lipid metabolism and management of reactive oxygen species. Peroxisome Biogenesis Factor (Peroxin, Pex) genes encode proteins essential to peroxisome biogenesis or function. In yeast and mammals, PEROXIN7 acts as a cytosolic receptor protein that targets a subset of enzymes for peroxisome matrix import.Proteins targeted by PEROXIN7 contain a peroxisome targeting sequence 2 (PTS2) motif. The PTS2 was not found in the D. melanogaster homologs of proteins that are PEROXIN7 targets in yeast or mammals, however comparative genomics suggest a Pex7 homolog is present in the D. melanogaster genome. Herein we report novel, tissue-specific patterns for transcription and translation of Pex7 in the D. melanogaster embryo that appear to be strongest in presumptive neuronal lineages. We also show that targeted somatic Pex7 knockout in neural precursors via targeted somatic CRISPR knockout affected survival of mutant embryos. Pex7 over-expression via Gal4-UAS also reduced adult survival but was not deleterious at the embryo stage. Notably, targeted somatic rescue of Pex7 in the neural precursors of Pex7 homozygous mutants also impaired embryo survival. We conclude that D. melanogaster has tissue-specific developmental requirements of Pex7 expression. This may be related to the requirement for peroxisome-mediated lipid synthesis in cells of the central nervous system.

Abstract 207: Unc-51-like Kinase 1 (ULK1) Plays A Crucial Role In Mitophagy In Cardiomyocytes

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Toshiro Saito ◽  
Junichi Sadoshima
Keyword(s):  
Glucose Deprivation ◽  
High Ratio ◽  
Control Mechanisms ◽  
Oxygen Species ◽  
Predominant Role ◽  
Mitochondrial Quality Control ◽  
Over Expression ◽  
Pathological Conditions

The mitochondrion is an essential organelle that supplies ATP in cardiomyocytes (CMs). However, damaged mitochondria are harmful via the production of reactive oxygen species and induction of apoptosis in pathological conditions. Therefore, quality of mitochondria should be controlled tightly through various mitochondrial quality control mechanisms. Mitochondrial autophagy (mitophagy) is considered an integral part of this mechanism, and recent investigations uncovered the role of PINK1 and Parkin in mitophagy. However, these observations were made under artificial conditions, such as over-expression of Parkin or treatment with CCCP, and thus the precise mechanism has not been fully elucidated in more pathophysiologically relevant conditions. Recent evidence suggests that mitophagy can take place independently of ATG7, a molecule essential for the conventional form of autophagy, and that this form of autophagy is ULK1-dependent. We investigated the role of ULK1 and ATG7 in mediating mitophagy using mitochondria-targeted Keima (Mito-Keima) in cultured rat neonatal CMs. Keima has a bimodal excitation spectrum peaking at 440 and 560 nm, corresponding to the neutral and acidic pH, respectively. In CMs transfected with Mito-Keima, the fluorescent dots with a high 560nm/440nm ratio represent the mitochondria incorporated into autolysosomes which indicate mitophagy. Here we report that ULK1 plays a more predominant role in glucose deprivation (GD) -induced mitophagy than ATG7. Control CMs exhibited 8.7±1.0 % of the area of high-ratio dots per cells after GD. Knockdown of ULK1 significantly reduced the area to 2.3±0.9 % in CMs after GD (p<0.01, vs sh-Control). The reduction was significantly greater in CMs with knockdown of ULK1 than that of ATG7 (7.0±1.6 %, p<0.05, sh-ULK1 vs sh-ATG7). In addition, knockdown of Beclin1 and Drp1 also significantly decreased the area of high-ratio dots (about 1.0 % and 0.5 %, respectively). Overexpression of ULK1 was sufficient to induce mitophagy without starvation, whereas that of ATG7 was not. These results suggest that ULK1, Beclin1 and Drp1 play an essential role in mediating GD-induced mitophagy in CMs.

Hypoxia-induced reactive oxygen species downregulate ETB receptor-mediated contraction of rat pulmonary arteries

2006 ◽  
Vol 290 (3) ◽  
pp. L570-L578 ◽  
Author(s):  
Xiaohua Wang ◽  
Mei Tong ◽  
Shashi Chinta ◽  
J. Usha Raj ◽  
Yuansheng Gao
Keyword(s):  
Reactive Oxygen Species ◽  
Pulmonary Arteries ◽  
Reactive Oxygen ◽  
Receptor Protein ◽  
Oxygen Species ◽  
Superoxide Anions ◽  
Type B ◽  
Etb Receptor ◽  
Normoxic Control

Production of reactive oxygen species (ROS) may be increased during hypoxia in pulmonary arteries. In this study, the role of ROS in the effect of hypoxia on endothelin (ET) type B (ETB) receptor-mediated vasocontraction in lungs was determined. In rat intrapulmonary (∼0.63 mm ID) arteries, contraction induced by IRL-1620 (a selective ETB receptor agonist) was significantly attenuated after 4 h of hypoxia (30 mmHg Po2) compared with normoxic control (140 mmHg Po2). The effect was abolished by tiron, a scavenger of superoxide anions, but not by polyethylene glycol (PEG)-conjugated catalase, which scavenges H2O2. The hypoxic effect on ETB receptor-mediated vasoconstriction was also abolished by endothelium denudation but not by nitro-l-arginine and indomethacin. Exposure for 4 h to exogenous superoxide anions, but not H2O2, attenuated the vasoconstriction induced by IRL-1620. Confocal study showed that hypoxia increased ROS production in pulmonary arteries that were scavenged by PEG-conjugated SOD. In endothelium-intact pulmonary arteries, the ETB receptor protein was reduced after 4 h of exposure to hypoxia, exogenous superoxide anions, or ET-1. BQ-788, a selective ETB receptor antagonist, prevented these effects. ET-1 production was stimulated in endothelium-intact arteries after 4 h of exposure to hypoxia or exogenous superoxide anions. This effect was blunted by PEG-conjugated SOD. These results demonstrate that exposure to hypoxia attenuates ETB receptor-mediated contraction of rat pulmonary arteries. A hypoxia-induced production of superoxide anions may increase ET-1 release from the endothelium and result in downregulation of ETB receptors on smooth muscle.

scholarly journals Peroxisome biogenesis and positioning

2010 ◽  
Vol 38 (3) ◽  
pp. 807-816 ◽  
Author(s):  
Alison Baker ◽  
Imogen A. Sparkes ◽  
Laura-Anne Brown ◽  
Catherine O'Leary-Steele ◽  
Stuart L. Warriner
Keyword(s):  
Endoplasmic Reticulum ◽  
Degradation Pathway ◽  
Matrix Proteins ◽  
Peroxisome Biogenesis ◽  
Environmental Signals ◽  
Targeting Signal ◽  
Membrane Bound ◽  
Plant Life Cycle ◽  
Peroxisome Membrane

Plant peroxisomes are extremely dynamic, moving and undergoing changes of shape in response to metabolic and environmental signals. Matrix proteins are imported via one of two import pathways, depending on the targeting signal within the protein. Each pathway has a specific receptor but utilizes common membrane-bound translocation machinery. Current models invoke receptor recycling, which may involve cycles of ubiquitination. Some components of the import machinery may also play a role in proteolytic turnover of matrix proteins, prompting parallels with the endoplasmic-reticulum-associated degradation pathway. Peroxisome membrane proteins, some of which are imported post-translationally, others of which may traffic to peroxisomes via the endoplasmic reticulum, use distinct proteinaceous machinery. The isolation of mutants defective in peroxisome biogenesis has served to emphasize the important role of peroxisomes at all stages of the plant life cycle.

The role of cell lineage in development

1985 ◽  
Vol 312 (1153) ◽  
pp. 3-19 ◽  
Keyword(s):  
Cell Fate ◽  
Cell Lineage ◽  
Early Embryo ◽  
Embryonic Cell ◽  
Evolutionary Divergence ◽  
Causative Role ◽  
Embryonic Cells ◽  
Developmental Potential ◽  
Cell Lineages

Studies of the role of cell lineage in development began in the latter part of the 19th century, fell into decline in the early part of the 20th, and were revived about 20 years ago. This recent revival was accompanied by the introduction of new and powerful analytical techniques. Concepts of importance for cell lineage studies include the principal division modes by which a cell may give rise to its descendant clone (proliferative, stem cell and diversifying); developmental determinacy , or indeterminacy , which refer to the degree to which the normal cleavage pattern of the early embryo and the developmental fate of its individual cells is, or is not, the same in specimen after specimen; commitment , which refers to the restriction of the developmental potential of a pluripotent embryonic cell; and equivalence group , which refers to two or more equivalently pluripotent cell clones that normally take on different fates but of which under abnormal conditions one clone can take on the fate of another. Cell lineage can be inferred to have a causative role in developmental cell fate in embryos in which induced changes in cell division patterns lead to changes in cell fate. Moreover, such a causative role of cell lineage is suggested by cases where homologous cell types characteristic of a symmetrical and longitudinally metameric body plan arise via homologous cell lineages. The developmental pathways of commitment to particular cell fates proceed according to a mixed typologic and topographic hierarchy, which appears to reflect an evolutionary compromise between maximizing the ease of ordering the spatial distribution of the determinants of commitment and minimizing the need for migration of differentially committed embryonic cells. Comparison of the developmental cell lineages in leeches and insects indicates that the early course of embryogenesis is radically different in these phyletically related taxa. This evolutionary divergence of the course of early embryogenesis appears to be attributable to an increasing prevalence of polyclonal rather than monoclonal commitment in the phylogenetic line leading from an annelid-like ancestor to insects.

An axial domain of HOM/Hox gene expression is formed by morphogenetic alignment of independently specified cell lineages in the leech Helobdella

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1839-1849 ◽  
Author(s):  
D. Nardelli-Haefliger ◽  
A.E. Bruce ◽  
M. Shankland
Keyword(s):  
Embryonic Stem ◽  
Cell Lineage ◽  
Homeobox Gene ◽  
Positional Information ◽  
The Other ◽  
Expression Domain ◽  
Hox Gene ◽  
Cell Lineages ◽  
High Level

The homeobox gene Lox2, a member of the HOM/Hox gene class, is expressed in a restricted domain along the anteroposterior (A-P) body axis of the leech Helobdella. The segmental tissues of the leech embryo arise from the parallel merger of five distinct and bilaterally paired cell lineages generated by embryonic stem cells or teloblasts. Injection of cell lineage tracers coupled with anti-LOX2 immunochemistry reveals that all five teloblast lineages generate central nervous system neurons that express the LOX2 protein, and that each lineage expresses LOX2 within a similar domain of body segments. Some lineally identified neurons display anti-LOX2 immunoreactivity over the entire expression domain, but the OM7 neuron has a distinctively high level of LOX2 expression, which is restricted to the seventh midbody ganglion. To ascertain the role of positional information in the axial patterning of LOX2 expression, we performed focal cell ablations that displaced one or another of the teloblast lineages out of segmental register with the other axial tissues. Such displacements brought about a corresponding shift in the LOX2 expression of the perturbed lineage, and had little or no effect on the LOX2 expression of the other, unperturbed lineages. This result indicates that the axial domain of LOX2 expression is not specified by positional cues acting coordinately across the various teloblast lineages, nor would it seem that the expression domain is imprinted from one lineage to the others. Rather, the different teloblast lineages acquire their axial patterns independently, and secondarily bring these patterns into alignment along the A-P axis through a process of morphogenetic assembly.

scholarly journals PAX3: A Molecule with Oncogenic or Tumor Suppressor Function Is Involved in Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ashok Arasu ◽  
Sengottuvelan Murugan ◽  
Musthafa Mohamed Essa ◽  
Thirunavukkarasu Velusamy ◽  
Gilles J. Guillemin
Keyword(s):  
Tumor Suppressor ◽  
Cell Fate ◽  
Cancer Progression ◽  
Tumor Suppressor Function ◽  
Aberrant Expression ◽  
Tissue Specific ◽  
Cell Lineages ◽  
Neurodevelopmental Disease ◽  
Potential Link

Metastasis is the most deadly aspect of cancer and results from acquired gene regulation abnormalities in tumor cells. Transcriptional regulation is an essential component of controlling of gene function and its failure could contribute to tumor progression and metastasis. During cancer progression, deregulation of oncogenic or tumor suppressive transcription factors, as well as master cell fate regulators, collectively influences multiple steps of the metastasis cascade, including local invasion and dissemination of the tumor to distant organs. Transcription factor PAX3/Pax3, which contributes to diverse cell lineages during embryonic development, plays a major role in tumorigenesis. Mutations in this gene can cause neurodevelopmental disease and the existing literature supports that there is a potential link between aberrant expression of PAX3 genes in adult tissues and a wide variety of cancers. PAX3 function is tissue-specific and could contribute to tumorigenesis either directly as oncogene or as a tumor suppressor by losing its function. In this review, we discuss comprehensively the differential role played by PAX3 in various tissues and how its aberrant expression is implicated in disease development. This review particularly highlights the oncogenic and tumor suppressor role played by PAX3 in different cancers and underlines the importance of precisely identifying tissue-specific role of PAX3 in order to determine its exact role in development of cancer.

Genetic control of extraembryonic cell lineages studied with tetraploiddiploid chimeric concepti

1998 ◽  
Vol 76 (6) ◽  
pp. 1017-1027
Author(s):  
Sergey Kupriyanov ◽  
Hélène Baribault
Keyword(s):  
Genetic Control ◽  
Cell Lineage ◽  
Genetically Engineered ◽  
Developmental Genetics ◽  
Tissue Formation ◽  
Cell Lineages ◽  
Lineage Differentiation ◽  
Aggregation Chimera ◽  
Extraembryonic Tissues

The first differentiation event during mammalian embryogenesis is the commitment of blastomeres to the trophectoderm cell lineage. Much remains to be learned about the genetic control of this first cell lineage commitment and the subsequent events underlying the differentiation of all extraembryonic cell lineages. Because of the unique features of intrauterine embryonic development, the study of embryogenesis in lower organisms has shed little light on mammalian extraembryonic lineage differentiation. Rather, two major methods in developmental genetics have contributed to our understanding of genetic control of extraembryonic cell lineages. First, abnormalities in extraembryonic tissues have been described in many genetically engineered mutant mouse lines. However, the histological description of these abnormalities does not demonstrate whether the observed defect is the primary cause of embryonic lethality. Second, tetraploid<–>diploid aggregation experiments have been used to generate chimeric concepti with distinct genotypes in the extraembryonic tissues and the embryo proper. This experimental approach has provided the definitive demonstration of the crucial role of several transcription factors, growth factors and cytoskeleton proteins in extraembryonic tissue formation. The present review summarizes the origin of tetraploid<–>diploid aggregation experiments and it usefulness for the study the genetic control of extraembryonic cell lineages.Key words: tetraploid, aggregation, chimera, extraembryonic cell lineages, placenta.

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