Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA118547 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations. expression data were collected from 6 CHM patients' monocytes and 4 CHM primary fibroblasts cultures, monocytes or FB from 5 normal age-matched subjects were used as a control
2010-02-21 | E-GEOD-17549 | biostudies-arrayexpress
Project description:Choroideremia (CHM) is a progressive X-linked retinopathy caused by mutations in the CHM gene, which encodes Rab escort protein-1 (REP-1), an escort protein involved in the prenylation of Rabs. Under-prenylation of certain Rabs, as a result of loss of function mutations in REP-1, could affect vesicular trafficking, exocytosis and secretion. To evaluate this hypothesis, intracellular vesicle transport, lysosomal acidification and rates of proteolytic degradation were studied in monocytes (CD14+ fraction) and primary skin fibroblasts from the nine age-matched controls and thirteen CHM patients carrying 10 different loss-of-function mutations.
2010-01-27 | GSE17549 | GEO
Project description:Recombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single codon mutations to the AAV2 rep gene on AAV2 production. Most beneficial variants are not observed in nature, indicating that improved production may require synthetic mutations. Additionally, the effects of AAV2 rep mutations were largely consistent across capsid serotypes, suggesting that production benefits are capsid independent. Our results provide a detailed sequence-to-function map that enhances our understanding of Rep protein function and lays the groundwork for Rep engineering and enhancement of large scale gene therapy production.
2023-02-28 | GSE226265 | GEO
Project description:To determine what genes are affect to the reduction in mutation frequency by 500 µGy gamma irradiation of Drosophila melanogaster. The strain is w[1118] (a loss of function mutant of compound eye pigment gene white with Canton-S background). Experiment Overall Design: 15 samples are analyzed. The control and four time course (5, 30, 60 and 90min), 3 Biological rep. (A to C).
2008-03-13 | E-GEOD-9552 | biostudies-arrayexpress
Project description:Normal neural development is essential for the formation of neuronal networks and brain function. cTAGE5/MEA6 plays a critical role in the secretion of proteins. However, its roles in the transport of non-secretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is essential for brain development and function. Conditional knockout of cTAGE5/MEA6 in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, synapse formation and/or maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the ER to Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines, but also the signaling pathways required for neuronal development. Since mutations in cTAGE5/MEA6 have been found in patients with Fahr’s disease, our study potentially also provides insight into the pathogenesis of this disorder.
2018-09-18 | PXD010386 | Pride
Project description:Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a fatal brain disorder featuring cerebellar neurodegeneration leading to spasticity and ataxia. ARSACS is caused by mutations in the SACS gene that encodes sacsin, a massive 4579 amino acid protein with multiple modular domains. Here we demonstrate that sacsin binds to microtubules and regulates microtubule dynamics. Loss of sacsin function in knockout cell lines, knockdown and knockout neurons, and patient fibroblasts leads to alterations in lysosomal transport, positioning, function and reformation following autophagy.
2022-10-15 | PXD033823 | Pride
Project description:CACNA1A loss-of-function mutations affect neurogenesis in different ways in human iPSC-derived neural models
| PRJNA1157468 | ENA
Project description:Cellular senescence is characterized by persistent cell cycle arrest, apoptosis resistance, and widespread changes in gene expression. Although the functional alterations in organelles like mitochondria and lysosomes are well characterized, senescence-associated changes in the structure and function of the Golgi apparatus remain poorly understood. The Golgi apparatus orchestrates intracellular transport processes that rely heavily on the coating of vesicles with Coatomer Protein Complex I (COPI) proteins (COPA, COPB1, COPB2, COPD, COPE, COPG1, and COPZ1). Based on an earlier RNA interference (RNAi) screen showing that silencing COPI subunits reduced extracellular vesicle (EV) uptake in human diploid WI-38 fibroblasts, and that EV uptake was diminished in senescent WI-38 cells, we sought to functionally analyze COPI proteins in senescent cells. In proliferating cells, individually silencing COPA, COPB1, COPB2, or COPD induced ATF4 production and disrupted autophagy, apoptosis, and cytokine signaling—hallmarks of impaired Golgi-to-ER transport—while individually silencing COPG1, COPE, or COPZ1 altered extracellular matrix organization and GTPase activity. Silencing of any COPI subunit reduced mitochondrial respiration and EV uptake. Proteomic analysis revealed that individual COPI proteins associate with both Golgi and endosomal components, supporting their role in vesicular trafficking. Importantly, the phenotypic effects observed in proliferating cells were not observed in senescent cells, which appeared refractory to further COPI reduction. Our findings underscore the distinct, multifunctional actions of individual COPI proteins and suggest that they are key factors in the intracellular transport networks that sustain homeostatic responses, which become attenuated during senescence.
2026-06-11 | GSE302417 | GEO
Project description:Affect of Socs2 loss-of-function on liver regeneration
| PRJNA225288 | ENA
Project description:The persistent supply of glucose in the retina is essential for underpinning ATP production to meet the retinal cell’s energy requirements essential for the vision. Glucose transporters mainly mediate the glucose supply and diffusion thorough the retinal vasculature, choroid/RPE and photoreceptor cells. While the physiological mechanisms behind glucose supply have been well studied and described, how glucose supply dysfunction contributes to the phenotype of retinal disease is poorly understood. Now we provide evidence that retinal energetic failure dependent by glucose supply defect explains large part of the phenotype of Choroideremia (CHM), an X-linked chorioretinal dystrophy caused by mutations in the Rab escort protein-1 (REP-1) gene. By interrogating the effect of REP-1 depletion in CHM, we found that alteration of glucose transporters GLUT-4 and GLUT-1 in the RPE/retina cells contribute to the CHM phenotype. REP-1 loss induces glucose-dependent bioenergetic deficiency, altering mitochondria morphology and function. By restoring both GLUTs expression and membrane translocation through pharmacological induction of phosphatidylinositol 3-Kinase pathway, we re-established the glucose uptake and its commitment towards RPE/retina both in vitro and in vivo. This study supports the notion that, in CHM, the absence of REP-1 causes an altered glucose uptake, which determines a deficit of energy compromising retinal cell homeostasis and function.
2026-05-20 | GSE299462 | GEO