The GARP Complex Is Involved in Intracellular Cholesterol Transport via Targeting NPC2 to Lysosomes

Wei, Jian; Zhang, Yingyu; Luo, Jie; Wang, Ju-Qiong; Zhou, Yüxia; Miao, Hong‐Hua; Shi, Xiongjie; Qu, Yuanzhi; Xu, Jie; Li, Bo-Liang; Song, Bao-Liang

doi:10.1016/j.celrep.2017.06.012

Cited by 50 publications

(44 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Consistent with this finding, mutation of the specific component of the GARP complex, Vps54, in human amyotrophic lateral sclerosis (ALS) patients and in wobbler mice was found to be associated with a dysregulation of energy metabolism . In wobbler mice, these energy metabolism defects were linked to a disturbance of cholesterol homeostasis, suggesting that the GARP complex may be involved in the regulation of cholesterol flux. However, this needs to be confirmed, because EARP and GARP complexes share one‐quarter of their components, such that affecting one complex may alter the other.…”

Section: Regulation Of Glucose and Lipid Metabolism Through The Endosmentioning

confidence: 61%

“…In addition to LDLR trafficking, endocytosis participates in the regulation of cholesterol flux within cells, which requires the function of Niemann‐Pick type C (NPC) proteins. Indeed, mutations of Vps53 prevent the proper sorting of NPC2 to lysosomes, causing cholesterol accumulation . Vps53 is a common component of two complexes, the endosome‐associated recycling protein (EARP) and the Golgi‐associated retrograde protein (GARP), which are implicated in the tethering of cargo‐containing carriers sorted from the endosomes to direct them either to the recycling compartments or the TGN, respectively (for review see Reference ).…”

Section: Regulation Of Glucose and Lipid Metabolism Through The Endosmentioning

confidence: 99%

See 1 more Smart Citation

Metabolic regulation through the endosomal system

Gilleron

Gerdes

Zeigerer

2019

Traffic

View full text Add to dashboard Cite

The endosomal system plays an essential role in cell homeostasis by controlling cellular signaling, nutrient sensing, cell polarity and cell migration. However, its place in the regulation of tissue, organ and whole body physiology is less well understood. Recent studies have revealed an important role for the endosomal system in regulating glucose and lipid homeostasis, with implications for metabolic disorders such as type 2 diabetes, hypercholesterolemia and non‐alcoholic fatty liver disease. By taking insights from in vitro studies of endocytosis and exploring their effects on metabolism, we can begin to connect the fields of endosomal transport and metabolic homeostasis. In this review, we explore current understanding of how the endosomal system influences the systemic regulation of glucose and lipid metabolism in mice and humans. We highlight exciting new insights that help translate findings from single cells to a wider physiological level and open up new directions for endosomal research.

show abstract

Section: Regulation Of Glucose and Lipid Metabolism Through The Endosmentioning

confidence: 61%

Section: Regulation Of Glucose and Lipid Metabolism Through The Endosmentioning

confidence: 99%

Metabolic regulation through the endosomal system

Gilleron

Gerdes

Zeigerer

2019

Traffic

View full text Add to dashboard Cite

show abstract

“…Their cellular components mainly included cytosol, nuclear speck, and cell-cell adhesion junction. The genes VPS53, ITGB8, ZNF736, and TTC26 play important roles in cholesterol transport in cardiac cells, mediating the interaction between cell-cell and cell-extracellular matrix, regulate transcription, and transport proteins [23][24][25]. Among them VPS53 and PHLDB2, GPATCH2, ITGB8, ZNF736, TTC26 exhibited opposite expressions in groups A, B, and C. This suggests that VPS53 and PHLDB2, GPATCH2, ITGB8, ZNF736, TTC26 might have opposite effects on some processes of the disease.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

Wang¹,

Chen

Zhang³

et al. 2020

BMC Cardiovasc Disord

View full text Add to dashboard Cite

Background: The current diagnostic methods and treatments still fail to lower the incidence of anthracyclineinduced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicityrelated abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Methods: Cardiotoxicity-related gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the Gene Expression Omnibus (GEO) database. The biomarker expression data of women with chemotherapyinduced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the micro RNAs (miRNAs) regulating the differential expressions. The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs. Then, the Gene Ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. Result: The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and Target Scan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain seven cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273 g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273 g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. The signaling pathway is mainly concentrated in TGF-β signaling pathway and adhesion signaling pathway. Conclusions: Changes in expression of hsa-miR-4638-3p and hsa-miR-1273 g-3p may contribute to the detection of anthracyclines induced cardiac toxicity, and their potential function may be related to TGF-β signaling pathway and adhesion signaling pathway.

show abstract

“…Their cellular components mainly included cytosol, nuclear speck, and cell-cell adhesion junction. The genes VPS53, ITGB8, ZNF736, and TTC26 play important roles in cholesterol transport in cardiac cells, mediating the interaction between cell-cell and cell-extracellular matrix, regulate transcription, and transport proteins [19][20][21]. Among them VPS53 and PHLDB2, GPATCH2, ITGB8, ZNF736, TTC26 exhibited opposite expressions in groups A, B, and C. This suggests that VPS53 and PHLDB2, GPATCH2, ITGB8, ZNF736, TTC26 might have opposite effects on some processes of the disease.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

Wang

Chen

Zhang

et al. 2019

Preprint

View full text Add to dashboard Cite

The current diagnostic methods and treatments still fail to lower the incidence of anthracyclineinduced cardiotoxicity effectively. In this study, we aimed to (1) analyze the cardiotoxicity-related genes after breast cancer chemotherapy in gene expression database and (2) carry out bioinformatic analysis to identify cardiotoxicity-related abnormal expressions, the biomarkers of such abnormal expressions, and the key regulatory pathways after breast cancer chemotherapy. Cardiotoxicityrelated gene expression data (GSE40447) after breast cancer chemotherapy was acquired from the GEO database. The biomarker expression data of women with chemotherapy-induced cardiotoxicity (group A), chemotherapy history but no cardiotoxicity (group B), and confirmatory diagnosis of breast cancer but normal ejection fraction before chemotherapy (group C) were analyzed to obtain the mRNA with differential expressions and predict the miRNAs regulating the differential expressions.The miRanda formula and functional enrichment analysis were used to screen abnormal miRNAs.Then, the gene ontology (GO) analysis was adapted to further screen the miRNAs related to cardiotoxicity after breast cancer chemotherapy. The data of differential analysis of biomarker expression of groups A, B, and C using the GSE40447-related gene expression profile database showed that there were 30 intersection genes. The differentially expressed mRNAs were predicted using the miRanda and TargetScan software, and a total of 2978 miRNAs were obtained by taking the intersections. Further, the GO analysis and targeted regulatory relationship between miRNA and target genes were used to establish miRNA-gene interaction network to screen and obtain 7 cardiotoxicity-related miRNAs with relatively high centrality, including hsa-miR-4638-3p, hsa-miR-5096, hsa-miR-4763-5p, hsa-miR-1273g-3p, hsa-miR6192, hsa-miR-4726-5p and hsa-miR-1273a.Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p had the highest centrality. The PCR verification results were consistent with those of the chip data. There are differentially expressed miRNAs in the peripheral blood of breast cancer patients with anthracycline cardiotoxicity. Among them, hsa-miR-4638-3p and hsa-miR-1273g-3p are closely associated with the onset of anthracycline cardiotoxicity in patients with breast cancer. Mining, integrating, and validating effective information resources of biological gene chips can provide a new direction for further studies on the molecular mechanism of 3 anthracycline cardiotoxicity.

show abstract

The GARP Complex Is Involved in Intracellular Cholesterol Transport via Targeting NPC2 to Lysosomes

Cited by 50 publications

References 62 publications

Metabolic regulation through the endosomal system

Metabolic regulation through the endosomal system

Bioinformatic analysis of peripheral blood miRNA of breast cancer patients in relation with anthracycline cardiotoxicity

Bioinformatic Analysis of Peripheral Blood miRNA of Breast Cancer Patients in Relation With Anthracycline Cardiotoxicity

Contact Info

Product

Resources

About