Biology subjects

Dai, W.

Publications and source records attributed to Dai, W..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

Cell type-specific translational regulation by Human DUS enzymes

Dihydrouridine is an abundant and conserved modified nucleoside present on tRNA, but characterization and functional studies of modification sites and associated DUS writer enzymes in mammals is lacking. Here we use a chemical probing strategy, RNABPP-PS, to identify 5-chlorouridine as an activity-based probe for human DUS enzymes. We map D modifications using RNA-protein crosslinking and chemical transformation and mutational profiling to reveal D modification sites on human tRNAs. Further, we knock out individual DUS genes in two human cell lines to investigate regulation of tRNA expression levels and codon-specific translation. We show that whereas D modifications are present across most tRNA species, loss of D only perturbs the translational function of a subset of tRNAs in a cell type-specific manner. Our work provides powerful chemical strategies for investigating D and DUS enzymes in diverse biological systems and provides insight into the role of a ubiquitous tRNA modification in translational regulation.

biochemistry↗

bioRxiv2023

Decoding Heterogenous Single-cell Perturbation Responses

Understanding diverse responses of individual cells to the same perturbation is central to many biological and biomedical problems. Current methods, however, do not precisely quantify the strength of perturbation responses and, more importantly, reveal new biological insights from heterogeneity in responses. Here we introduce the perturbation-response score (PS), based on constrained quadratic optimization, to quantify diverse perturbation responses at a single-cell level. Applied to single-cell transcriptomes of large-scale genetic perturbation datasets (e.g., Perturb-seq), PS outperforms existing methods for quantifying partial gene perturbation responses. In addition, PS presents two major advances. First, PS enables large-scale, single-cell-resolution dosage analysis of perturbation, without the need to titrate perturbation strength. By analyzing the dose-response patterns of over 2,000 essential genes in Perturb-seq, we identify two distinct patterns, depending on whether a moderate reduction in their expression induces strong downstream expression alterations. Second, PS identifies intrinsic and extrinsic biological determinants of perturbation responses. We demonstrate the application of PS in contexts such as T cell stimulation, latent HIV-1 expression, and pancreatic cell differentiation. Notably, PS unveiled a previously unrecognized, cell-type-specific role of coiled-coil domain containing 6 (CCDC6) in guiding liver and pancreatic lineage decisions, where CCDC6 knockouts drive the endoderm cell differentiation towards liver lineage, rather than pancreatic lineage. The PS approach provides an innovative method for dose-to-function analysis and will enable new biological discoveries from single-cell perturbation datasets. One sentence summaryWe present a method to quantify diverse perturbation responses and discover novel biological insights in single-cell perturbation datasets.

bioinformatics↗

bioRxiv2023

CD36-Pyruvate Kinase M2 Signaling Promotes Macrophage Phagocytosis Through Mitochondrial Reactive Oxygen Species

Macrophage efferocytosis, the process by which phagocytes engulf and remove apoptotic cells (ACs), plays a critical role in maintaining tissue homeostasis. Efficient efferocytosis prevents secondary necrosis, mitigates chronic inflammation, and impedes atherosclerosis progression. However, the regulatory mechanisms of efferocytosis under atherogenic conditions remain poorly understood. We previously demonstrated that oxidized LDL (oxLDL), an atherogenic lipoprotein, induces mitochondrial reactive oxygen species (mtROS) in macrophages via CD36. In this study, we demonstrate that macrophage mtROS facilitate continual efferocytosis through a positive feedback mechanism. However, oxLDL disrupts continual efferocytosis by dysregulating the internalization of ACs. This disruption is mediated by an overproduction of mtROS. Mechanistically, oxLDL/CD36 signaling promotes the translocation of cytosolic PKM2 to mitochondria, facilitated by the chaperone GRP75. Mitochondrial PKM2 then binds to Complex III of the electron transport chain, inducing mtROS production. This study elucidates a novel regulatory mechanism of efferocytosis in atherosclerosis, providing potential therapeutic targets for intervention. SUMMARYMacrophages clear apoptotic cells through a process called efferocytosis, which involves mitochondrial ROS. However, the atherogenic oxidized LDL overstimulates mitochondrial ROS via the CD36-PKM2 pathway, disrupting continual efferocytosis. This finding elucidates a novel molecular mechanism that explains defects in efferocytosis, driving atherosclerosis progression.

immunology↗

bioRxiv2023

Normative Birth Weight Variation is Associated with White Matter Connectivity in Full-Term Neonates

ImportanceVariation in birth weight, an indicator of fetal growth, has been prospectively associated with both alterations in brain development and developmental delays in cognitive and language domains. However, studies examining birth weight variation and white matter development in the brain typically test these associations in infants that are preterm or very low birth weight, leaving potential normative associations in full term infants unclear. ObjectiveHere, we test prospective associations between birth weight variation in the normative range (> 2.5 kg and <4.5 kg) and white matter connectivity in full-term neonates. Further, the main objective includes testing associations between normative birth weight variation and cognitive and language developmental scores at 18 months, and if white matter connectivity that is related to birth weight variation is further associated with cognitive language development. We hypothesized, greater normative birth weight would be associated with higher white matter connectivity controlling for gestational age, particularly in thalamic, inferior frontal, and middle temporal connectivity. Further, we predicted greater connectivity for these tracts would be associated with higher scores for cognitive (thalamic) and language development (inferior and middle temporal) at 18 months of age. DesignThe study was an observational longitudinal design of data from the Developing Human Connectome Project (dHCP). Birth weight was measured at the birth of the child, white matter connectivity was measured as neonates (mean=40.07 weeks, SD=1.14), and cognitive/language outcomes were measured at 18 months of age. SettingThe dHCP data was collected at the Evelina Newborn Imaging Centre, Evalina London Childrens Hospital between 2015 and 2019. ParticipantsA sub-sample of the full dHCP was tested. These participants were full-term neonates with birth weight variation in the normative range (> 2.5 kg and < 4.5 kg). Participants also had to have usable diffusion-weighted imaging data as neonates and cognitive/language developmental assessments collected at 18 months (n=323). Exposure(s)The study participants were all born at full-term and in the normative birth weight range. Main Outcome(s) and Measure(s)The study had two main outcomes: white matter connectivity at the neonatal timepoint and cognitive/language developmental scores at 18 months. White matter connectivity was calculated from diffusion-weighted data for the whole-brain. Cognitive/language developmental scores were measured using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) at 18 months. ResultsUsing a Network-Based Statistic (NBS) approach, we found widespread associations between normative birth weight variation and white matter connectivity in full-term neonates, primarily in the positive direction for the right middle occipital gyrus and left supplementary motor area. Conclusions and RelevanceWhile investigations have been focused on the extreme ends of the birth weight spectrum, we find evidence that there is a robust association between birth weight and white matter connectivity even within the normative birth weight range. As normative birth weight variation and regions of white matter associated with birth weight were further associated with language development scores at 18 months, our results suggest the birth weight to white matter pathway may be an underlying pathway between birth weights association with language development. Key PointsO_ST_ABSQuestionC_ST_ABSAre variations in normative birth weight associated with white matter connectivity and cognitive/language outcomes in infancy? FindingsGreater normative birth weight is associated with greater white matter organization across a widespread network of connections in the neonatal brain. Greater white matter organization in this network for neonates has a positive prospective with expressive language development at 18 months of age. MeaningEven variations within the normative birth weight range have robust associations with early white matter development and can be prospectively linked to language development.

neuroscience↗

bioRxiv2023

Tip60-mediated Rheb acetylation links palmitic acid with mTORC1 activation and insulin resistance

Differences in dietary fatty acid saturation impact glucose homeostasis and insulin sensitivity in vertebrates. Excess dietary intake of saturated fatty acids (SFAs) induces glucose intolerance and metabolic disorders. In contrast, unsaturated fatty acids (UFAs) elicit beneficial effects on insulin sensitivity. However, it remains elusive how SFAs and UFAs signal differentially toward insulin signaling to influence glucose homeostasis. Here, using a croaker model, we report that dietary palmitic acid (PA), but not oleic acid or linoleic acid, leads to dysregulation of mTORC1 signaling which provokes systemic insulin resistance and glucose intolerance. Mechanistically, using croaker primary myocytes, mouse C2C12 myotubes and HEK293T cells, we show that PA-induced mTORC1 activation is dependent on mitochondrial fatty acid {beta} oxidation. Notably, PA profoundly elevates acetyl-CoA derived from mitochondrial fatty acid {beta} oxidation which intensifies Tip60-mediated Rheb acetylation. Subsequently, the induction of Rheb acetylation facilitates hyperactivation of mTORC1 which enhances serine phosphorylation of IRS1 and simultaneously inhibits transcription of IRS1 through impeding TFEB nuclear translocation, leading to impairment of insulin signaling. Furthermore, targeted abrogation of acetyl-CoA produced from fatty acid {beta} oxidation or Tip60-mediated Rheb acetylation by pharmacological inhibition and genetic knockdown rescues PA-induced insulin resistance. Collectively, this study reveals a conserved acetylation-dependent mechanistic insight for understanding the link between fatty acids and insulin resistance, which may provide a potential therapeutic avenue to intervene in the development of T2D.

cell biology↗

bioRxiv2023

Hypoxia Bi-directionally Regulates Gut Vascular Barrier through HIF-1α-dependent Mechanism in vitro

ObjectiveThe gut vascular barrier (GVB) is the key checkpoint for pathogens to enter the blood circulation through the intestine, which is crucial for maintaining the intestinal barrier function. However, the effect and molecular mechanism of hypoxia on GVB remains unclear. Here, we show a role of the transcription factor hypoxia inducible factor-1 (HIF-1) in hypoxia-induced bi-directional regulation of GVB. Approach and ResultsAn in vitro GVB model composed of rat intestinal microvascular endothelial cells was studied. Evans blue-albumin efflux assay showed that the experimentally severe hypoxia induced by cobalt chloride (500 M, 24 h) markedly disrupted the GVB in vitro, while mild hypoxia induced by cobalt chloride (500 M, 6 h) evidently enhanced the GVB, revealing hypoxia-induced bi-directional regulation of the GVB for the first-time. Importantly, knockdown of HIF-1 largely abolished the bi-directional changes of GVB caused by hypoxia. Furthermore, experimentally severe hypoxia exacerbated the inflammatory GVB disruption induced by LPS or TNF-, while the mild hypoxia promoted the repair. ConclusionCollectively, our data indicate that hypoxia bi-directionally regulates GVB in a HIF-1-dependent manner.

cell biology↗

bioRxiv2023

Use of Artificial Intelligence for Automated Detection and Surveillance of Red Imported Fire Ants Nests

The red imported fire ant, Solenopsis invicta Buren is a destructive invasive species that has spread around the world. Early detection of S. invicta nests is critical for effective monitoring and control in invaded regions. This study presents a novel surveillance system for S. invicta nests combining artificial intelligence and robotic dogs. The system was designed with intelligent recognition algorithms to accurately identify S. invicta nests. With a precision rate of 95%, the system yielded efficient detection of S. invicta nests with increased sensitivity and low missing and false discovery rates, which can aid or even replace humans in locating and delivering pesticides to fire ant nests in open fields to effective control of this invasive pest.

ecology↗

bioRxiv2023

Rescue of proteotoxic stress and neurodegeneration by the Zn2+ transporter ZIP7

Proteotoxic stress drives numerous degenerative diseases. In response to misfolded proteins, cells adapt by activating the unfolded protein response (UPR), including endoplasmic reticulum-associated protein degradation (ERAD). However persistent stress triggers apoptosis. Enhancing ERAD is a promising therapeutic approach for protein misfolding diseases. From plants to humans, loss of the Zn2+ transporter ZIP7 causes ER stress, however the mechanism is unknown. Here we show that ZIP7 enhances ERAD and that cytosolic Zn2+ is limiting for deubiquitination of client proteins by the Rpn11 Zn2+ metalloproteinase as they enter the proteasome in Drosophila and human cells. ZIP7 overexpression rescues defective vision caused by misfolded rhodopsin in Drosophila. Thus ZIP7 overexpression may prevent diseases caused by proteotoxic stress, and existing ZIP inhibitors may be effective against proteasome-dependent cancers. One-Sentence SummaryZn2+ transport from the ER to the cytosol promotes deubiquitination and proteasomal degradation of misfolded proteins and prevents blindness in a fly neurodegeneration model.

cell biology↗

bioRxiv2023

FASN-deficiency induces a cytosol-to-mitochondria citrate flux to mitigate detachment-induced oxidative stress

Fatty acid synthase (FASN) maintains de novo lipogenesis (DNL) to support rapid growth in most proliferating cancer cells. Lipogenic acetyl-CoA is primarily produced from carbohydrates but can arise from glutamine-dependent reductive carboxylation under hypoxia. Here we show that reductive carboxylation also occurs in the absence of DNL in cells with defective FASN. In this state, reductive carboxylation was mainly catalyzed by isocitrate dehydrogenase-1 (IDH1) in the cytosol, but IDH1-generated citrate was not used for DNL. Metabolic flux analysis (MFA) revealed that FASN-deficiency induced a net cytosol-to-mitochondria citrate flux through citrate transport protein (CTP). A similar pathway was previously shown to mitigate detachment-induced mitochondrial reactive oxygen species (mtROS) in anchorage-independent tumor spheroids. We further demonstrate that FASN-deficient cells acquire resistance to oxidative stress in a CTP- and IDH1-dependent manner. Together with the reduced FASN activity in tumor spheroids, these data indicate that anchorage-independent malignant cells trade FASN-supported rapid growth for a cytosol-to-mitochondria citrate flux to gain redox capacity against detachment-induced oxidative stress.

cancer biology↗

bioRxiv2023

ImmuneMirror: a Machine Learning-based Integrative Pipeline and Web Server for Neoantigen Prediction

Neoantigens are derived from tumors but are absent in normal tissues. Emerging evidence suggests that neoantigens can stimulate tumor-specific T-cell-mediated antitumor immune responses, and neoantigens are potential immunotherapy targets. We developed ImmuneMirror as a stand-alone open-source pipeline (https://github.com/weidai2/ImmuneMirror/) and a web server (http://immunemirror.hku.hk/App/) incorporating a balanced random forest model for neoantigen prediction and prioritization; the model was trained and tested using known immunogenic neopeptides collected from 19 published studies. The area under the curve (AUC) of our model was 0.87. We utilized ImmuneMirror in gastrointestinal tract cancers and discovered a subgroup of microsatellite instability-high (MSI-H) colorectal cancer (CRC) patients with a low neoantigen load but a high tumor mutation burden (TMB>10 mutations per Mbp). Although the efficacy of PD-1 blockade has been demonstrated in advanced MSI-H patients, almost half of such patients do not respond well. Our study may identify MSI-H patients who do not benefit from this treatment. Additionally, the neopeptide YMCNSSCMGV-TP53G245V, derived from a hotspot mutation restricted by HLA-A02, was identified as an actionable target in esophageal squamous cell carcinoma (ESCC). This is the largest study to comprehensively evaluate neoantigen prediction models using experimentally validated neopeptides. Our results demonstrate the reliability and effectiveness of ImmuneMirror for neoantigen prediction.

bioinformatics↗

bioRxiv2022

PilD mutant is a new cheater in Pseudomonas aeruginosa quorum-sensing evolution

Pathogen virulence is largely driven by the evolution and adaptation of the genome. LasR is a master regulator of quorum-sensing (QS) system. The QS-inactive LasR-null mutant regains QS activation in a laboratory evolution experiment through obtaining mutations in mexT, a gene encoding transcriptional regulator. How the QS-active LasR-MexT mutant continuously evolves is still unknown. Here we passaged the LasR-MexT mutant in casein broth and monitored its evolutionary trajectory. By examining the proteolytic phenotype of isolated single colonies, we found a protease-negative subpopulation arising from the parental population. The whole genome sequencing analysis revealed that these protease-negativ colonies bear mutations in pilD gene. In accordance with its role as a prepilin peptidase of type IV system, PilD mutants are defective in twitching motility. In conclusion, we identified a new PilD mutant cheater that evolved from the parental LasR-MexT mutant population. Our work demonstrates that population evolution is highly dynamics, with arising of distinct subpopulations containing different social behaviors.

microbiology↗

bioRxiv2022

A chromosome-level genome assembly of the Asian corn borer, Ostrinia furnacalis, reveals repeated origin of a Leipdopteran neo-W chromosome from the Z chromosome

We built a chromosome-level genome assembly of the Asian corn borer, Ostrinia furnacalis Guenee (Lepidoptera: Pyralidae, Pyraloidea), an economically important pest in corn, from a female, including both the Z and W chromosome. Despite deep conservation of the Z chromosome across Lepidoptera, our chromosome-level W assembly reveals little conservation with available W chromosome sequence in related species or with the Z chromosome, consistent with a non-canonical origin of the W chromosome. The W chromosome has accumulated significant repetitive elements and experienced rapid gene gain from the remainder of the genome, with most genes exhibiting pseudogenization after duplication to the W. The genes that retain significant expression are largely enriched for functions in DNA recombination, the nucleosome, chromatin and DNA binding, likely related to meiotic and mitotic processes within the female gonad.

evolutionary biology↗

bioRxiv2022

When two is a crowd - Structural mapping of PEAK pseudokinase interactions identifies 14 3 3 as a molecular switch for PEAK3/Crk signaling.

PEAK pseudokinases regulate cell migration, invasion and proliferation by recruiting key signaling proteins to the cytoskeleton. Despite lacking catalytic activity, alteration in their expression level is associated with several aggressive cancers. Here, we elucidate new molecular details of key PEAK signaling interactions with the adapter proteins CrkII and Grb2 and the scaffold protein 14-3-3. Our findings rationalize why the dimerization of PEAK proteins has a crucial function in signal transduction and provide biophysical and structural data to unravel binding specificity within the PEAK interactome. We identify a conserved high affinity 14-3-3 motif on PEAK3 and demonstrate its role as a molecular switch to regulate CrkII binding. Together, our studies provide a detailed structural snapshot of PEAK interaction networks and further elucidate how PEAK proteins, especially PEAK3, act as dynamic scaffolds that exploit adapter proteins to control signal transduction in cell growth/motility and cancer.

biochemistry↗

bioRxiv2022

Discovery of unknown quorum-sensing reprogramming factors in Pseudomonas aeruginosa using a dual-acting-gene-blocking approach

LasR is a master regulator of quorum-sensing (QS) in Pseudomonas aeruginosa. LasR-null mutants commonly appear in lung isolates from chronically infected cystic fibrosis (CF) patients. However, numerous such CF isolates have a QS-active phenotype, but factors underlying QS-reprogramming in LasR-null mutants remain largely unknown. Mutations in the transcriptional regulator gene mexT are well known to be responsible for QS-reprogramming in a laboratory LasR-null mutant strain, however, simultaneous occurrence of lasR and mexT mutations is rare in CF isolates. To identify QS-reprogramming determinants, we developed an experimental evolution approach, for which a QS-inactive LasR null mutant with an extra copy of mexT was engineered. In such a strain, spontaneous single mexT mutations are expected to have no or little phenotypic consequences. This novel method, named "targeted gene duplication followed by mutant screening" (TGD-MS), resulted in the identification of QS-active revertants with mutations in genes other than mexT. We characterized a QS-active revertant with a point mutation in rpoA, a gene encoding the -subunit of RNA polymerase. QS activation in this mutant was found to be associated with the down-regulated expression of mexEF-oprN efflux pump genes. Our study therefore uncovers a new functional role for RpoA in regulating QS activity. Furthermore, our results suggest that a regulatory circuit controlling the expression of the mexEF-oprN operon is critical for QS-reprogramming. In conclusion, our study reports on the identification of non-MexT proteins associated with QS-reprogramming in a laboratory strain, shedding light on possible QS activation mechanisms in clinical P. aeruginosa isolates.

microbiology↗

bioRxiv2021

Sensory convergence in the world s largest cavefish diversification: patterns of neuromast evolution, distribution and associated behaviour in Sinocyclocheilus

The genus Sinocyclocheilus represents the largest freshwater cavefish genus in the world. This emerging model system is endemic to the southern Chinese karstic landscape, and demonstrates multiple adaptations for caves (troglomorphism), with eye-degeneration being the most pronounced. The less-apparent lateral line system, which is often expanded in cave-dwellers, has been studied in other cavefish systems, but never in the context of this diversification. Here we investigated the distribution and evolution of cephalic neuromasts in 26 Sinocyclocheilus species. We used live-staining and behavioural assays, and interpreted results in a phylogenetic context. We show that asymmetry in neuromast features and the rate of evolution is greater in cave-adapted species. Ancestral state reconstructions show that most Sinocyclocheilus are right-biased with some scatter, and show convergence of neuromast phenotypes. There is substantial variation in cephalic neuromast distribution patterns between and (to a lesser extent) within species. Behavioural assays show blind species have a distinctive wall-following behaviour. We explain these patterns in the context of the deep evolutionary history associated with this karstic region, other organismal traits, and habitat occupation of these remarkable diversifications of fishes. Interestingly, some of these neuromast patterns and behaviour show convergence with other phylogenetically distant cavefish systems.

zoology↗

bioRxiv2021

The first crested duck genome reveals clues to genetic compensation and crest cushion formation

The Chinese crested (CC) duck is a unique indigenous waterfowl breed with a phenotypic crest trait that affects its high survival rate. Therefore, the CC duck is an ideal model to investigate the genetic compensation response to maintain genetic stability. In the present study, we first generated a chromosome-level genome of CC ducks. Comparative genomics revealed genes related to tissue repair, immune function, and tumors were under strong positive selection, which suggested that these adaptive changes might enhance cancer resistance and immune response to maintain the genetic stability of CC ducks. We sub-assembled a Chinese spot-billed duck genome and detected genome-assembled structure variants among three ducks. Functional analysis revealed that a large number of structural variants were related to the immune system, which strongly suggests the occurrence of genetic compensation in the anti-tumor and immune systems to further support the survival of CC ducks. Moreover, we confirmed that the CC duck originated from the mallard ducks. Finally, we revealed the physiological and genetic basis of crest traits and identified a causative mutation in TAS2R40 that leads to crest formation. Overall, the findings of this study provide new insights into the role of genetic compensation in adaptive evolution.

genomics↗

bioRxiv2021

Single-cell analysis of early chick hypothalamic development reveals that hypothalamic cells are induced from prethalamic-like progenitors.

The hypothalamus is an evolutionarily ancient brain region that regulates many innate behaviors, but its development is still poorly understood. To identify molecular mechanisms controlling hypothalamic specification and patterning, we used single-cell RNA-Seq to profile multiple stages of early hypothalamic development in the chick. We observe that hypothalamic neuroepithelial cells are initially induced from prethalamic-like cells. Two distinct hypothalamic progenitor populations emerge later, which give rise to paraventricular/mammillary and tuberal hypothalamus. At later developmental stages, the regional organization of the chick and mouse hypothalamus closely resembles one another. This study identifies selective markers for major subdivisions of the developing chick hypothalamus and many uncharacterized candidate regulators of hypothalamic patterning and neurogenesis. As proof of concept for the power of the dataset, we demonstrate that follistatin, a novel prethalamic progenitor-like marker, inhibits hypothalamic induction. This study both clarifies the organization of the early developing hypothalamus and identifies novel molecular mechanisms controlling hypothalamic induction, regionalization, and neurogenesis. HighlightsO_LIEarly hypothalamic development was profiled in chick using scRNA-Seq and multiplexed HCR. C_LIO_LIHypothalamic cells are induced from prethalamic-like neuroepithelial cells. C_LIO_LIDistinct paraventricular/mammillary and tuberal progenitor populations emerge later, and hypothalamic organization is evolutionarily conserved. C_LIO_LIPrethalamic progenitor-derived follistatin inhibits hypothalamic specification. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/438683v1_ufig1.gif" ALT="Figure 1"> View larger version (73K): org.highwire.dtl.DTLVardef@18ac4c2org.highwire.dtl.DTLVardef@17bb90aorg.highwire.dtl.DTLVardef@1b17cceorg.highwire.dtl.DTLVardef@178e769_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2021

Collective border cell migration requires the zinc transporter Catsup to limit endoplasmic reticulum stress

Collective cell migration is critical for normal development, wound healing, and in tumor progression and metastasis. Border cells in the Drosophila ovary provide a genetically tractable model to identify molecular mechanisms that drive this important cell behavior. In an unbiased screen for defects in border cell migration in mosaic clones, we identified a mutation in the catsup gene. Catsup, the Drosophila ortholog of Zip7, is a large, multifunctional, transmembrane protein of the endoplasmic reticulum (ER), which has been reported to negatively regulate catecholamine biosynthesis, to regulate Notch signaling, to function as a zinc transporter, and to limit ER stress. Here we report that catsup knockdown caused ER stress in border cells and that ectopic induction of ER stress was sufficient to block migration. Notch and EGFR trafficking were also disrupted. Wild type Catsup rescued the migration defect but point mutations known to disrupt the zinc ion transport of Zip7 did not. We conclude that migrating cells are particularly susceptible to defects in zinc transport and ER homeostasis.

cell biology↗