Biology subjects

Wen, J.

Publications and source records attributed to Wen, J..

At least 109 records · Page 6Linked to original sources

bioRxiv2021

Spatiotemporal cytokinin signaling imaging reveals IPT3 function in nodule development in Medicago truncatula

Most legumes can establish a symbiotic association with soil rhizobia that triggers the development of root nodules. These nodules host the rhizobia and allow them to fix nitrogen efficiently. The perception of bacterial lipo-chitooligosaccharide (LCO) signal in the epidermis initiates a signaling cascade that allows rhizobial intracellular infection in the root and de-differentiation and activation of cell division that gives rise to the nodule. Nodule organogenesis and rhizobial infection need to be coupled in space and time for successful nodulation. The plant hormone cytokinin (CK) acts as an essential positive regulator of nodule organogenesis, and specific CK receptors are required for nodule formation. Temporal regulation of tissue-specific CK signaling and biosynthesis in response to LCOs or Sinorhizobium meliloti inoculation in Medicago truncatula remains poorly understood. In the present study, using a fluorescence-based CK sensor (TCSn::nls:tGFP), we performed a high-resolution tissue-specific temporal characterization of the CK responses sequential activation during root infection and nodule development in M. truncatula after inoculation with S. meliloti. Loss-of-function mutants of the CK-biosynthetic gene ISOPENTENYL TRANSFERASE 3 (IPT3) showed impairment of nodulation, suggesting that IPT3 is required for nodule development in M. truncatula. Simultaneous live imaging of pIPT3::tdTOMATO and the CK sensor showed that IPT3 induction in the root stele at the base of nodule primordium contributes to CK biosynthesis, which in turn promotes expression of positive regulators of nodule organogenesis in M. truncatula. One-sentence summaryHigh-resolution spatiotemporal imaging of cytokinin signaling reveals IPT3 function during indeterminate nodule development in Medicago truncatula

plant biology↗

bioRxiv2021

Phylogenomic insights into the divergent history and hybridization within the East Asian endemic Abelia (Caprifoliaceae)

Background and AimsAbelia (Caprifoliaceae) is a small genus with five species, including one man-made hybrid and several natural hybrids. The genus has a discontinuous distribution in mainland China, Taiwan Island, and the Ryukyu islands, providing a model system to explore mechanisms of species dispersal in the East Asian flora. However, the current phylogenetic relationships within Abelia remain uncertain. MethodsIn this study, we reconstructed phylogenetic relationships within Abelia using nuclear loci generated by target enrichment and plastomes from genome skimming. Divergence time estimation, ancestral area reconstruction, and ecological niche modelling (ENM) were used to examine the diversification history of Abelia. Key ResultsWe found extensive cytonuclear discordance across the genus. By integrating lines of evidence from molecular phylogenies, divergence times, and morphology, we propose to merge A. macrotera var. zabelioides into A. uniflora. Network analyses suggested that there have been widespread and multiple hybridization events among Abelia species. These hybridization events may have contributed to the speciation mechanism and resulted in a high observed morphological diversity. The diversification of Abelia began in the early Eocene, followed by A. chinensis var. ionandra colonizing the island of Taiwan in the Middle Miocene. The ENM results suggested an expansion of climatically suitable areas during the Last Glacial Maximum and range contraction during the Last Interglacial. Disjunction between the Himalayan-Hengduan Mountain region (HHM) and the island of Taiwan is most likely the consequence of topographic isolation and postglacial contraction. ConclusionsWe used genomic data to reconstruct the phylogeny of Abelia and found a clear pattern of reticulate evolution in the group. In addition, our results support shrinkage of postglacial range and the heterogeneity of the terrain have led to the disjunction of the mainland China-Taiwan island. This study provides important new insights into the speciation process and taxonomy of Abelia.

evolutionary biology↗

bioRxiv2021

Target enrichment improves phylogenetic resolution in the genus Zanthoxylum (Rutaceae) and indicates both incomplete lineage sorting and hybridization events

Background and aimsZanthoxylum L. is the only pantropical genus within Rutaceae, with a few species native to temperate eastern Asia and North America. Efforts using Sanger sequencing failed to resolve the backbone phylogeny of Zanthoxylum. In this study, we employed target enrichment high-throughput sequencing to improve resolution. Gene trees were examined for concordance and sectional classifications of Zanthoxylum were evaluated. Off-target reads were investigated to identify putative single-copy markers for bait refinement, and low-copy markers for evidence of putative hybridization events. MethodsWe developed a custom bait set for target enrichment of 745 exons in Zanthoxylum and applied it to 45 Zanthoxylum species and one Tetradium species as the outgroup. Illumina reads were processed via the HybPhyloMaker pipeline. Phylogenetic inferences were conducted using coalescent and concatenated methods. Concordance was assessed using quartet sampling. Off-target reads were assembled and putative single- and low-copy genes were extracted. Additional phylogenetic analyses were performed based on these alignments. Key resultsFour major clades are supported within Zanthoxylum: the African clade, the Z. asiaticum clade, the Asian-Pacific-Australian clade, and the American-eastern Asian clade. While overall support has improved, regions of conflict are similar to those previously observed. Gene tree discordances indicate a hybridization event in the ancestor of the Hawaiian lineage, and incomplete lineage sorting for the American backbone. Off-target putative single-copy genes largely confirm on-target results, and putative low-copy genes provide additional evidence for hybridization in the Hawaiian lineage. Only two of the five sections of Zanthoxylum are resolved as monophyletic. ConclusionTarget enrichment is suitable to assess phylogenetic relationships in Zanthoxylum. Our phylogenetic analyses reveal that current sectional classifications need revision. Quartet tree concordance indicates several instances of reticulate evolution. Off-target reads are proven useful to identify additional phylogenetically informative regions for bait refinement or gene tree based approaches.

evolutionary biology↗

bioRxiv2021

The plant circadian clock gene LHY influences Medicago truncatula nodulation

Legumes house nitrogen-fixing endosymbiotic rhizobia in specialized polyploid cells within root nodules, which are factories of metabolic activity. We discovered that the circadian clock-associated transcriptional factor LATE ELONGATED HYPOCOTYL (LHY) affects nodulation in Medicago truncatula. By carrying out expression analysis of transcripts over time in nodules we found that the clock enables coordinated control of metabolic and regulatory processes linked to nitrogen fixation. Rhythmic transcripts in root nodules include a subset of Nodule-specific Cysteine Rich peptides (NCRs) that have the LHY-bound conserved Evening Element in their promoters. Until now, studies have suggested that NCRs act to regulate bacteroid differentiation and keep the rhizobial population in check. However, these conclusions came from the study of a few members of this very large gene family that has complex diversified spatio-temporal expression. We suggest that rhythmic expression of NCRs may be important for temporal coordination of bacterial activity with the rhythms of the plant host, in order to ensure optimal symbiosis. HighlightsO_LIThe circadian clock-associated transcriptional factor LATE ELONGATED HYPOCOTYL (LHY) impacts on successful Medicago truncatula-rhizobial symbiosis C_LIO_LIThe plant clock coordinates rhythmic patterns of metabolic and regulatory activity in nodules and drives rhythmic expression of a subset of Nodule-specific Cysteine Rich (NCR) genes. C_LIO_LIRhythmic expression of NCRs may be important for temporal coordination of bacterial activity with plant host rhythms to ensure optimal symbiosis. C_LI

plant biology↗

bioRxiv2021

Super interactive promoters provide insight into cell type-specific regulatory networks in blood lineage cell types

Existing studies of chromatin conformation have primarily focused on potential enhancers interacting with gene promoters. By contrast, the interactivity of promoters per se, while equally critical to understanding transcriptional control, has been largely unexplored, particularly in a cell type-specific manner for blood lineage cell types. In this study, we leverage promoter capture Hi-C data across a compendium of blood lineage cell types to identify and characterize cell type-specific super-interactive promoters (SIPs). Notably, promoter-interacting regions (PIRs) of SIPs are more likely to overlap with cell type-specific ATAC-seq peaks and GWAS variants for relevant blood cell traits than PIRs of non-SIPs. Further, SIP genes tend to express at a higher level in the corresponding cell type, and show enriched heritability of relevant blood cell trait(s). Importantly, this analysis shows the potential of using promoter-centric analyses of chromatin spatial organization data to identify biologically important genes and their regulatory regions.

genetics↗

bioRxiv2021

Capturing single-copy nuclear genes, organellar genomes, and nuclear ribosomal DNA from deep genome skimming data for plant phylogenetics: A case study in Vitaceae

With the decreasing cost and availability of many newly developed bioinformatics pipelines, next-generation sequencing (NGS) has revolutionized plant systematics in recent years. Genome skimming has been widely used to obtain high-copy fractions of the genomes, including plastomes, mitochondrial DNA (mtDNA), and nuclear ribosomal DNA (nrDNA). In this study, through simulations, we evaluated optimal (minimum) sequencing depth and performance for recovering single-copy nuclear genes (SCNs) from genome skimming data, by subsampling genome resequencing data and generating 10 datasets with different sequencing coverage in silico. We tested the performance of the four datasets (plastome, nrDNA, mtDNA, and SCNs) obtained from genome skimming based on phylogenetic analyses of the Vitis clade at the genus-level and Vitaceae at the family-level, respectively. Our results showed that optimal minimum sequencing depth for high-quality SCNs assembly via genome skimming was about 10x coverage. Without the steps of synthesizing baits and enrichment experiments, we showcase that deep genome skimming (DGS) is effective for capturing large datasets of SCNs, in addition to plastomes, mtDNA, and entire nrDNA repeats, and may serve as an economical alternative to the widely used target enrichment Hyb-Seq approach.

evolutionary biology↗

bioRxiv2021

BnaA03.WRKY28, interacting with BnaA09.VQ12, acts as a brake factor of activated BnWRKY33-mediated resistance outburst against Sclerotinia sclerotiorum in Brassica napus

Sclerotinia sclerotiorum causes substantial damage to the growth of Brassica napus (rapeseed) and makes a significant loss of crop yield. The plant innate immune system may be the primary solution to defense against S. sclerotiorum for rapeseed. Here, we identify that BnWRKY33, a transcription factor in the innate immune pathway, can be rapidly phosphorylated and activated by the MAPK cascade after rapeseed is infected with S. sclerotiorum. In the MAPK cascade, activated BnaA03.MKK4 phosphorylates and activates BnaA06.MPK3 and BnaC03.MPK3. The activated BnMPK3 acts on the substrate BnWRKY33 to enhance its transcriptional activity and trigger a transcriptional burst of BnWRKY33, which helps plants effectively resist the pathogenic fungi by enhancing the expression of phytoalexin synthesis-related genes. With constant infection, BnaA03.WRKY28 and BnaA09.VQ12 are induced, and BnaA03.WRKY28 physically interacts with BnaA09.VQ12 to form a protein complex. BnaA03.WRKY28 preferentially binds to the promoter of BnWRKY33 with the help of BnaA09.VQ12. Compared with activated BnWRKY33, BnaA03.WRKY28 has a lower transcriptional activity on downstream BnWRKY33, which leads to weaker resistance against S. sclerotiorum for rapeseed in the later stage of infection. Furthermore, the induced BnaA03.WRKY28 may promote axillary bud activity and axillary meristem initiation by regulating the expression of branching-related genes (such as BnBRC1), thus promoting the formation of branches in the leaf axils. One-sentence summaryUnder constant infection by Sclerotinia sclerotiorum, BnaA03.WRKY28 interacts with BnaA09.VQ12 and takes precedence over phosphorylated BnWRKY33 to bind to the BnWRKY33 promoter, thereby weakening resistance but promoting branching.

plant biology↗

bioRxiv2021

Plants export 2-monopalmitin and supply both fatty acyl and glyceryl moieties to arbuscular mycorrhizal fungi

Arbuscular mycorrhizal fungi (AMF) rely on their host plants to provide them with fatty acids (FA), but the precise form(s) in which they are supplied is still unclear. Here we show that ectopic expression of the transcription factor REQUIRED FOR ARBUSCULAR MYCORRHIZATION 1 (RAM1) can drive secretion of 2-monoacylglycerols (2MGs) from Medicago truncatula roots and that their main FA moiety is palmitic acid, although myristic acid and stearic acid were also detected. RAM1-dependent 2MG secretion requires the acyl-acyl carrier protein thioesterase FATM, the glycerol-3-phosphate (G3P) acyltransferase RAM2 and the ATP binding cassette transporter STR. Furthermore, 14C glycerol labelling experiments using mycorrhizal M. truncatula roots that are deficient in glycerol kinase, FAD-dependent G3P dehydrogenase and the G3P acyltransferase RAM2 suggest that most of the glyceryl moieties in Rhizophagus irregularis storage lipids are provided by their host plant through the 2MG pathway. Taken together, our data support the hypothesis that the plant exports 2MGs across the peri-arbuscular membrane in mycorrhizal roots and that the AMF receive and utilise both the FA and glyceryl moieties to make their storage lipids.

plant biology↗

bioRxiv2020

SnapHiC: a computational pipeline to map chromatin contacts from single cell Hi-C data

Single cell Hi-C (scHi-C) analysis has been increasingly used to map the chromatin architecture in diverse tissue contexts, but computational tools to define chromatin contacts at high resolution from scHi-C data are still lacking. Here, we describe SnapHiC, a method that can identify chromatin loops at high resolution and accuracy from scHi-C data. We benchmark SnapHiC against HiCCUPS, a common tool for mapping chromatin contacts in bulk Hi-C data, using scHi-C data from 742 mouse embryonic stem cells. We further demonstrate its utility by analyzing single-nucleus methyl-3C-seq data from 2,869 human prefrontal cortical cells. We uncover cell-type-specific chromatin loops and predict putative target genes for non-coding sequence variants associated with neuropsychiatric disorders. Our results suggest that SnapHiC could facilitate the analysis of cell-type-specific chromatin architecture and gene regulatory programs in complex tissues.

bioinformatics↗

bioRxiv2020

Fxr signaling and microbial metabolism of bile salts in the zebrafish intestine

Bile salt synthesis, secretion into the intestinal lumen, and resorption in the ileum occurs in all vertebrate classes. In mammals, bile salt composition is determined by host and microbial enzymes, affecting signaling through the bile salt-binding transcription factor Farnesoid X receptor (Fxr). However, these processes in other vertebrate classes remain poorly understood. We show that key components of hepatic bile salt synthesis and ileal transport pathways are conserved and under control of Fxr in zebrafish. Zebrafish bile salts consist primarily of a C27 bile alcohol and a C24 bile acid which undergo multiple microbial modifications including bile acid deconjugation that augments Fxr activity. Using single-cell RNA sequencing, we provide a cellular atlas of the zebrafish intestinal epithelium and uncover roles for Fxr in transcriptional and differentiation programs in ileal and other cell types. These results establish zebrafish as a non-mammalian vertebrate model for studying bile salt metabolism and Fxr signaling.

physiology↗

bioRxiv2020

A phylogenomic perspective on gene tree conflict and character evolution in Caprifoliaceae using target enrichment data, with Zabelioideae recognized as a new subfamily

The use of diverse datasets in phylogenetic studies aiming for understanding evolutionary histories of species can yield conflicting inference. Phylogenetic conflicts observed in animal and plant systems have often been explained by hybridization, incomplete lineage sorting (ILS), or horizontal gene transfer. Here, we employed target enrichment data, species tree and species network approaches to infer the backbone phylogeny of the family Caprifoliaceae, while distinguishing among sources of incongruence. We used 713 nuclear loci and 46 complete plastome sequence data from 43 samples representing 38 species from all major clades to reconstruct the phylogeny of the family using concatenation and coalescence approaches. We found significant nuclear gene tree conflict as well as cytonuclear discordance. Additionally, coalescent simulations and phylogenetic species network analyses suggested putative ancient hybridization among subfamilies of Caprifoliaceae, which seems to be the main source of phylogenetic discordance. Ancestral state reconstruction of six morphological characters revealed some homoplasy for each character examined. By dating the branching events, we inferred the origin of Caprifoliaceae at approximately 66.65 Ma in the late Cretaceous. By integrating evidence from molecular phylogeny, divergence times, and morphology, we herein recognize Zabelioideae as a new subfamily in Caprifoliaceae. This work shows the necessity of using a combination of multiple approaches to identify the sources of gene tree discordance. Our study also highlights the importance of using data from both nuclear and chloroplast genomes to reconstruct deep and shallow phylogenies of plants.

evolutionary biology↗

bioRxiv2020

Molecular basis for cysteine oxidation by Plant Cysteine Oxidases from Arabidopsis thaliana

Plant Cysteine Oxidases (PCOs) play important roles in controlling the stability of Group VII ethylene response factors (ERF-VIIs) via N-Arg/degron pathway through catalyzing the oxidation of their N-Cys for subsequent Arginyl-tRNA--protein transferase 1 (ATE1) mediated arginine installation. Here we presented structures of PCO2, PCO4, and PCO5 from Arabidopsis thaliana (AtPCOs) and examined their in vitro activity by MS. On the basis of Tris-bound AtPCO2, we modelled the Cys-bound AtPCO2 structure and identified key residues involved in N-Cys oxidation. Alanine substitution of potential N-Cys interaction residues impaired the activity of AtPCO5 remarkably. The structural research, complemented by mutagenesis and mass spectrometry experiments, not only uncovers the substrate recognition and catalytic mode by AtPCOs, but also sheds light on the future design of potent inhibitors for plant cysteine oxidases.

molecular biology↗

bioRxiv2020

Cevipabulin-tubulin complex reveals a novel agent binding site on α-tubulin and provides insights into microtubule dynamic instability

Microtubule, composed of {beta}-tubulin heterodimers, remains as one of the most popular anticancer targets for decades. To date, anti-microtubule drugs are mainly functionally divided into microtubule-destabilizing and microtubule-stabilizing agents while microtubule- or tubulin-degradation agents are rarely reported. Six known binding sites on tubulin dimer are identified with five sites on {beta}-tubulin and only one site on -tubulin (pironetin site), hinting compounds binding to -tubulin are less well characterized. Cevipabulin, a microtubule-active antitumor clinical candidate, is widely accepted as a microtubule-stabilizing agent by binding to the vinblastine site. Our X-ray crystallography study reveals that, in addition binding to the vinblastine site, cevipabulin also binds to a novel site on -tubulin (named the seventh site) which located near the nonexchangeable GTP. Interestingly, we find the binding of cevipabulin to the seventh site induces tubulin degradation. As the non-exchangeable GTP has structural role and is important for the stability of tubulin dimers, we propose and confirm the tubulin degradation mechanism as: Cevipabulin at the seventh site puts the T5 loop outward to make the non-exchangeable GTP exchangeable, which reduces the stability of tubulin and results in its destabilization and degradation. Our results confirm a novel agent binding site on -tubulin and shed light on the development of tubulin degraders as a new generation of anti-microtubule drugs targeting this novel site.

cell biology↗

bioRxiv2020

Analyses of Biomarker Traits in Diverse UK Biobank Participants Identify Associations Missed by European-centric Analysis Strategies

Despite the dramatic underrepresentation of non-European populations in human genetics studies, researchers continue to exclude participants of non-European ancestry, even when these data are available. This practice perpetuates existing research disparities and can lead to important and large effect size associations being missed. Here, we conducted genome-wide association studies (GWAS) of 31 serum and urine biomarker quantitative traits in African (n=9354), East Asian (n=2559) and South Asian (n=9823) UK Biobank participants ancestry. We adjusted for all known GWAS catalog variants for each trait, as well as novel signals identified in European ancestry UK Biobank participants alone. We identify 12 novel signals in African ancestry and 3 novel signals in South Asian participants (p<1.61 x 10-10). Many of these signals are highly plausible and rare in Europeans (1% or lower minor allele frequency), including cis pQTLs for the genes encoding serum biomarkers like gamma-glutamyl transferase and apolipoprotein A, PIEZ01 and G6PD variants with impacts on HbA1c through likely erythocytic mechanisms, and a coding variant in GPLD1, a gene which cleaves GPI-anchors, associated with normally GPI-anchored protein alkaline phosphatase in serum. This work illustrates the importance of using the genetic data we already have in diverse populations, with many novel discoveries possible in even modest sample sizes.

genetics↗

bioRxiv2020

An Antioxidant Enzyme Therapeutic for COVID-19

The COVID-19 pandemic has taken a significant toll on people worldwide, and there are currently no specific antivirus drugs or vaccines. We report herein a therapeutic based on catalase, an antioxidant enzyme that can effectively breakdown hydrogen peroxide and minimize the downstream reactive oxygen species, which are excessively produced resulting from the infection and inflammatory process. Catalase assists to regulate production of cytokines, protect oxidative injury, and repress replication of SARS-CoV-2, as demonstrated in human leukocytes and alveolar epithelial cells, and rhesus macaques, without noticeable toxicity. Such a therapeutic can be readily manufactured at low cost as a potential treatment for COVID-19.

biochemistry↗

bioRxiv2020

A common human variant of GIPR improves systemic glucose homeostasis in a sexual dimorphic manner

Glucose-dependent insulinotropic polypeptide (GIP) has a role in controlling postprandial metabolic tone. In humans, a GIP receptor (GIPR) variant (Q354, rs1800437) is associated with a lower body mass index (BMI) and increased risk for Type 2 Diabetes. To isolate the contribution of GIPR in metabolic control, we generated a mouse model of the GIPR-Q354 variant (GIPR-Q350 mice). Female GIPR-Q350 mice are leaner than littermate controls, and male GIPR-Q350 mice are resistant to diet-induced obesity, in line with the association of the variant with reduced BMI in humans. GIPR-Q350 mice of both sexes are more glucose tolerant and exhibit an increased sensitivity to GIP. Postprandial GIP levels are reduced in GIPR-Q350 mice, revealing feedback regulation that balances the increased sensitivity of GIP target tissues to secretion of GIP from intestinal endocrine cells. The increased GIP sensitivity is recapitulated ex vivo during glucose stimulated insulin secretion assays in islets. Generation of cAMP in islets downstream of GIPR activation is not affected by the Q354 substitution. However, post-activation traffic of GIPR-Q354 variant in {beta}-cells is altered, characterized by enhanced intracellular dwell time and increased localization to the Trans-Golgi Network (TGN). Consequently, our data link altered intracellular traffic of the GIPR-Q354 variant with GIP control of metabolism. We propose that this change in spatiotemporal signaling underlies the physiologic effects of GIPR-Q350/4 and GIPR-E350/4 in mice and humans. These findings contribute to a more complete understanding of the impact of GIPR-Q354 variant on glucose homeostasis that could perhaps be leveraged to enhance pharmacologic targeting of GIPR for the treatment of metabolic disease.

physiology↗

bioRxiv2020

Immunity-and-Matrix-Regulatory Cells Derived from Human Embryonic Stem Cells Safely and Effectively Treat Mouse Lung Injury and Fibrosis

Lung injury and fibrosis represent the most significant outcomes of severe and acute lung disorders, including COVID-19. However, there are still no effective drugs to treat lung injury and fibrosis. In this study, we report the generation of clinical-grade human embryonic stem cells (hESCs)-derived immunity- and matrix-regulatory cells (IMRCs) produced under good manufacturing practice (GMP) requirements, that can treat lung injury and fibrosis in vivo. We generate IMRCs by sequentially differentiating hESCs with serum-free reagents. IMRCs possess a unique gene expression profile distinct from umbilical cord mesenchymal stem cells (UCMSCs), such as higher levels of proliferative, immunomodulatory and anti-fibrotic genes. Moreover, intravenous delivery of IMRCs inhibits both pulmonary inflammation and fibrosis in mouse models of lung injury, and significantly improves the survival rate of the recipient mice in a dose-dependent manner, likely through paracrine regulatory mechanisms. IMRCs are superior to both primary UCMSCs and FDA-approved pirfenidone, with an excellent efficacy and safety profile in mice and monkeys. In light of public health crises involving pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), our findings suggest that IMRCs are ready for clinical trials on lung disorders.

cell biology↗

bioRxiv2020

Insulin promoted mobilization of GLUT4 from a perinuclear storage site requires RAB10.

Insulin controls glucose uptake into muscle and fat cells by inducing a net redistribution of GLUT4 from intracellular storage to the plasma membrane (PM). The TBC1D4-RAB10 signaling module is required for insulin-stimulated GLUT4 translocation to the PM, although where it intersects GLUT4 traffic was unknown. Here we demonstrate that TBC1D4-RAB10 functions to control GLUT4 mobilization from a Trans Golgi Network (TGN) storage compartment, establishing that insulin, in addition to regulating the PM proximal effects of GLUT4-containing vesicles docking to and fusion with the PM, also directly regulates the behavior of GLUT4 deeper within the cell. We also show that GLUT4 is retained in an element/domain of the TGN from which newly synthesized lysosomal proteins are targeted to the late endosomes and the ATP7A copper transporter is translocated to the PM by elevated copper. Insulin does not mobilize ATP7A nor does copper mobilize GLUT4. Consequently, GLUT4 intracellular sequestration and mobilization by insulin is achieved, in part, through utilizing a region of the TGN devoted to specialized cargo transport in general rather than being specific for GLUT4. Our results define GLUT4-containing region of the TGN as a sorting and storage site from which different cargo are mobilized by distinct signals.

cell biology↗