Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA283840 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Comparative haploid genetic screens to annotate common and specialized genes required for the biogenesis of individual GPI anchored proteins. SEC62 and SEC63 were required for proper PrP targeting, and were dispensable for CD59. CD59 however, required a GPI side chain modification for maturation, in addition to the aspartyl intramembrane cleaving protease: SPPL3.
2015-05-13 | GSE68796 | GEO
Project description:We performed neuron and glia specific knockdown of PIG-A in Drosophila to understand the molecular defects that occur with loss of GPI anchored proteins. PIG-A encodes an enzyme responsible for the first step in GPI anchor biosynthesis. Loss of PIG-A in neurons and glia results in different neurological defects.
2023-10-31 | GSE241512 | GEO
Project description:The SEL1L-HRD1 protein complex of endoplasmic reticulum (ER)-associated degradation (ERAD) plays indispensable roles for many physiological processes in a substrate-specific manner; however, the nature of endogenous substrates remains largely elusive. Here we have developed a unique proteomics strategy based on the intrinsic property of the SEL1L-HRD1 ERAD complex to identify potential endogenous ERAD substrates in human kidney cell line HEK293T and mouse brown adipocytes. Over 100 potential substrates involved in many cellular processes, including both membrane and luminal proteins regardless of their glycosylation and disulfide bond status, are identified in each cell type, among which 34 are shared. We further uncover SEL1L-HRD1 ERAD as a suppressor of the biogenesis of glycosylphosphatidylinositol (GPI)-anchored proteins via degrading a key subunit of the GPI-transamidase complex known as phosphatidylinositol glycan anchor biosynthesis class K protein (PIGK). Lastly, several PIGK disease variants are highly unstable and quickly degraded by SEL1L-HRD1 ERAD. This study shows the most effective way to identify cell type-specific proteome-wide potential endogenous SEL1L-HRD1 substrates, and uncovers a new function of SEL1L-HRD1 ERAD in the biogenesis and disease pathogenesis associated with GPI-anchored proteins
2023-12-17 | PXD041803 | Pride
Project description:The SEL1L-HRD1 protein complex of endoplasmic reticulum (ER)-associated degradation (ERAD) plays indispensable roles for many physiological processes in a substrate-specific manner; however, the nature of endogenous substrates remains largely elusive. Here we have developed a unique proteomics strategy based on the intrinsic property of the SEL1L-HRD1 ERAD complex to identify potential endogenous ERAD substrates in human kidney cell line HEK293T and mouse brown adipocytes. Over 100 potential substrates involved in many cellular processes, including both membrane and luminal proteins regardless of their glycosylation and disulfide bond status, are identified in each cell type, among which 34 are shared. We further uncover SEL1L-HRD1 ERAD as a suppressor of the biogenesis of glycosylphosphatidylinositol (GPI)-anchored proteins via degrading a key subunit of the GPI-transamidase complex known as phosphatidylinositol glycan anchor biosynthesis class K protein (PIGK). Lastly, several PIGK disease variants are highly unstable and quickly degraded by SEL1L-HRD1 ERAD. This study shows the most effective way to identify cell type-specific proteome-wide potential endogenous SEL1L-HRD1 substrates, and uncovers a new function of SEL1L-HRD1 ERAD in the biogenesis and disease pathogenesis associated with GPI-anchored proteins
2023-12-17 | PXD041882 | Pride
Project description:The glycosylphosphatidylinositol (GPI) biosynthetic pathway in the endoplasmic reticulum (ER) is crucial for generating GPI-anchored proteins (GPI-APs), which are translocated to the cell surface and play a vital role in cell signaling and adhesion. This study focuses on two integral components of the GPI pathway, the PIGL and PIGF proteins, and their significance in trophoblast biology. We show that GPI pathway mutations impact on placental development impairing the development of the syncytiotrophoblast (SynT), and especially the SynT-II layer, which is essential for the establishment of the definitive nutrient exchange area within the placental labyrinth. CRISPR/Cas9 knockout of Pigl and Pigf in mouse trophoblast stem cells (mTSC) confirms the role of these GPI enzymes in syncytiotrophoblast differentiation. Mechanistically, impaired GPI-AP generation induces an excessive unfolded protein response (UPR) in the ER in mTSCs growing in stem cell conditions, akin to what is observed in human preeclampsia. Remarkably, the transcriptomic profile of Pigl- and Pigf-deficient cells separates human patient placental samples into preeclampsia and control groups suggesting an involvement of Pigl and Pigf in establishing a preeclamptic gene signature. Upon differentiation, the impairment of the GPI pathway hinders the induction of WNT signaling for early SynT-II development. Our study unveils the pivotal role of GPI biosynthesis in early placentation and uncovers a new preeclampsia gene expression profile associated with mutations in the GPI biosynthesis pathway, providing novel molecular insights into placental development with implications for enhanced patient stratification and timely interventions.
2024-05-19 | GSE266153 | GEO
Project description:Glycosylphosphatidylinositol (GPI)-anchored proteins play crucial roles in various enzyme activities, cell signaling and adhesion, and immune responses. ZNT type zinc transporter proteins mobilize cytosolic zinc to the extracellular space and intracellular compartments. Here, we report that the early secretory pathway ZNTs [ZNT5-ZNT6 heterodimers (ZNT5-6) and ZNT7 homodimers (ZNT7)], which supply zinc into the lumen of organelles, are essential for GPI-anchored protein expression on the cell surface. Loss of ZNT5-6 and ZNT7 zinc transport functions results in a significant reduction of GPI-anchored proteins similar to that of mutant cells lacking phosphatidylinositol glycan anchor biosynthesis (PIG) genes. Disrupted ZNT5 and ZNT7 genes in medaka fish show touch-insensitive phenotypes similar to those of zebrafish PIG mutants. These findings provide a previously unappreciated insight into the regulation of GPI-anchored protein expression and of protein quality control in the early secretory pathway.
2022-05-04 | PXD032172 | Pride
Project description:GPI anchors many proteins to the cell surface. GPI precursor has three mannoses, all of which are modified by ethanolamine-phosphate (EthN-P). It has been believed that EthN-P on the third mannose is always used as a bridge to the protein and EthN-P on the second mannose is removed after GPI is attached to the protein. In fact, several GPI-anchored proteins are not appreciably reduced on cells defective in PIGG, which transfers EthN-P to the second mannose. Nevertheless, mutations in PIGG cause neuronal abnormalities. Here, we show that EthN-P on the second mannose is used as a preferential bridge for several GPI-anchored proteins. Our data modifies the current view of GPI anchors and provides mechanistic basis of PIGG deficiencies.
2022-05-31 | PXD029851 | Pride
Project description:GPI anchors many proteins to the cell surface. GPI precursor has three mannoses, all of which are modified by ethanolamine-phosphate (EthN-P). It has been believed that EthN-P on the third mannose is always used as a bridge to the protein and EthN-P on the second mannose is removed after GPI is attached to the protein. In fact, several GPI-anchored proteins are not appreciably reduced on cells defective in PIGG, which transfers EthN-P to the second mannose. Nevertheless, mutations in PIGG cause neuronal abnormalities. Here, we show that EthN-P on the second mannose is used as a preferential bridge for several GPI-anchored proteins. Our data modifies the current view of GPI anchors and provides mechanistic basis of PIGG deficiencies.
2022-05-31 | PXD029850 | Pride