Subjects: Biology >> Biophysics submitted time 2016-05-12
Abstract： What is a number? The number sense hypothesis suggests that numerosity is "a primary visual property" like color, contrast, or orientation. However, exactly what attribute of a stimulus is the primary visual property and determines numbers in the number sense? To verify the invariant nature of numerosity perception, we manipulated the numbers of items connected/enclosed in arbitrary and irregular forms while controlling for low-level features (e.g., orientation, color, and size). Subjects performed discrimination, estimation, and equality judgment tasks in a wide range of presentation durations and across small and large numbers. Results consistently show that connecting/enclosing items led to robust numerosity underestimation, with the extent of underestimation increasing monotonically with the number of connected/enclosed items. In contrast, grouping based on color similarity had no effect on numerosity judgment. We propose that numbers or the primitive units counted in numerosity perception are influenced by topological invariants, such as connectivity and the inside/outside relationship. Beyond the behavioral measures, neural tuning curves to numerosity in the intraparietal sulcus were obtained using functional MRI adaptation, and the tuning curves showed that numbers represented in the intraparietal sulcus were strongly influenced by topology.
Peer Review Status:
Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-11
Abstract： Long noncoding RNA (lncRNA) is an emerging category of transcript, and comprises the majority of the transcriptome of various complex organisms. The biological functions of only a handful of lncRNAs have been investigated in detail, showing involvement in a wide range of biological processes through different functional paradigms. However, most lncRNAs remain to be identified. Many lncRNAs are predicted to function, often preferentially, in the nervous system, potentially playing roles in mediating neural functions such as development, behavior, and cognition. To examine the biological significance and potential mechanisms of the remaining unknown neural lncRNAs, certain tractable model organisms, such as Drosophila, can provide advantages including the use of numerous genetic tools. Herein, we summarize recent progress on the in vivo or potential functions of Drosophila lncRNAs, in particular, behavior and development-related lncRNAs.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-11
Liu Ying
Mo Wei-Chuan
Fu Jing-Peng
Liu Ying
He Rong-Qiao
Fu Jing-Peng
Liu Ying
He Rong-Qiao
Ding Hai-Min
Hua Qian
Abstract： It has been established that exposure in the hypomagnetic field (HMF), which is one of the environmental factor of outer space, has adverse effects on animal and human behavior and brain function. Thus, it is necessary to develop appropriate counteract strategy to avoid the HMF-induced risks to the health of the astronauts during long-term and long-distance manned space mission. However, the physical and mental effects of the HMF in details still await systematic evaluation and the underlying mechanism remains elusive, so far. In this study, we constructed an HMF animal rearing system (<500 nT) and examined the effects of one-month HMF exposure on the circadian behavior, pain response and emotions in adult male C57BL/6 mice (4 similar to 6 weeks old, (20 +/- 2) g). The control animals were reared in the geomagnetic field (GMF). The HMF-exposed animals exhibited a prolonged alteration of the circadian drinking rhythm and a decrease in general activity, accompanied with an increase in thermal hyperalgesia. But the HMF did not induce obvious depression-like and anxiety-related behaviors. The serum noradrenalin concentration in HMF-exposed mice significantly decreased. These findings indicate that the HMF disturbs the behavior rhythm and the function of endocrine system, which probably leads to the subsequently weakened activities of the animal.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-11
Abstract： Humidity is one of the most important factors that determines the geographical distribution and survival of terrestrial animals. The ability to detect variation in humidity is conserved across many species. Here, we established a novel behavioral assay that revealed the thirsty Drosophila exhibits strong hygrotactic behavior, and it can locate water by detecting humidity gradient. In addition, exposure to high levels of moisture was sufficient to elicit proboscis extension reflex behavior in thirsty flies. Furthermore, we found that the third antennal segment was necessary for hygrotactic behavior in thirsty flies, while arista was required for the avoidance of moist air in hydrated flies. These results indicated that two types of hygroreceptor cells exist in Drosophila: one located in the third antennal segment that mediates hygrotactic behavior in thirst status, and the other located in arista which is responsible for the aversive behavior toward moist air in hydration status. Using a neural silencing screen, we demonstrated that synaptic output from the mushroom body alpha/beta surface and posterior neurons was required for both hygrotactic behavior and moisture-aversive behavior.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-12
Shang, Congping
Liu, Zhihui
Chen, Zijun
Shi, Yingchao
Wang, Qian
Liu, Su
Li, Dapeng
Cao, Peng
Shang, Congping
Chen, Zijun
Shi, Yingchao
Abstract： The fear responses to environmental threats play a fundamental role in survival. Little is known about the neural circuits specifically processing threat-relevant sensory information in the mammalian brain. We identified parvalbumin-positive (PV+) excitatory projection neurons in mouse superior colliculus (SC) as a key neuronal subtype for detecting looming objects and triggering fear responses. These neurons, distributed predominantly in the superficial SC, divergently projected to different brain areas, including the parabigeminal nucleus (PBGN), an intermediate station leading to the amygdala. Activation of the PV+ SC-PBGN pathway triggered fear responses, induced conditioned aversion, and caused depression-related behaviors. Approximately 20% of mice subjected to the fear-conditioning paradigm developed a generalized fear memory.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-11
Abstract： Exposure of pregnant females to strong prenatal stress generally induces psychotic-like behavioral impairments in their offspring. In contrast to strong stress exposure, mild prenatal stress exposure (MPSE) has been reported to increase the vulnerability of the nervous system to adverse environmental stimuli. However, the impacts of MPSE on treatment with antipsychotic medication have not been well investigated. In addition, although commonly utilized in animal experiments, the potential influences of injections per se on animal behavior have not been evaluated. Here, we investigated how MPSE, postnatal injections and olanzapine (OLZ) treatment might interact to affect the behavior of rats. Pregnant female rats were exposed to mild stress or left undisturbed during the last week of gestation. Their offspring were divided into three sub-groups and subjected to injections with saline or OLZ (2 mg/kg) on postnatal days (PDs) 7, 9 and 11 or were left undisturbed without injection. Social and olfactory discrimination tests were performed during adolescent (PD 35) and adult (PD 60) periods. Total exploratory time and the degree of preference in the discrimination tests were measured. We found that postnatal injections changed the degree of preference in adolescent prenatally stressed rats but had no effect on the degree of preference in the non-stressed rats. OLZ treatment increased the social exploratory time in the non-stressed rats during the adolescent and adult periods. However, these enhancing effects were diminished in the prenatally stressed rats. Our results indicate that MPSE could contribute to the behavioral changes induced by adverse stimuli such as postnatal injections and could reduce the treatment effects of antipsychotic medication.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Cell Biology submitted time 2016-05-12
Abstract： Mitochondrial calcium uniporter (MCU) is a conserved Ca2+ transporter at mitochondrial in eukaryotic cells. However, the role of MCU protein in oxidative stress-induced cell death remains unclear. Here, we showed that ectopically expressed MCU is mitochondrial localized in both HeLa and primary cerebellar granule neurons (CGNs). Knockdown of endogenous MCU decreases mitochondrial Ca2+ uptake following histamine stimulation and attenuates cell death induced by oxidative stress in both HeLa cells and CGNs. We also found MCU interacts with VDAC1 and mediates VDAC1 overexpression-induced cell death in CGNs. This finding demonstrates that MCU-VDAC1 complex regulates mitochondrial Ca2+ uptake and oxidative stress-induced apoptosis, which might represent therapeutic targets for oxidative stress related diseases.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-11
Abstract： Growing evidence suggests a strong association between cardiovascular risk factors and incidence of Alzheimer disease (AD). Asymmetric dimethylarginine (ADMA), the endogenous nitric oxide synthase inhibitor, has been identified as an independent cardiovascular risk factor and is also increased in plasma of patients with AD. However, whether ADMA is involved in the pathogenesis of AD is unknown. In this study, we found that ADMA content was increased in a transgenic Caenorhabditis elegans beta-amyloid (A beta) overexpression model, strain CL2006, and in human SH-SY5Y cells overexpressing the Swedish mutant form of human A beta precursor protein (APPsw). Moreover, ADMA treatment exacerbated A beta-induced paralysis and oxidative stress in CL2006 worms and further elevated oxidative stress and A beta secretion in APPsw cells. Knockdown of type 1 protein arginine N-methyltransferase to reduce ADMA production failed to show a protective effect against A beta toxicity, but resulted in more paralysis in CL2006 worms as well as increased oxidative stress and A beta secretion in APPsw cells. However, overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) to promote ADMA degradation significantly attenuated oxidative stress and A beta secretion in APPsw cells. Collectively, our data support the hypothesis that elevated ADMA contributes to the pathogenesis of AD. Our findings suggest that strategies to increase DDAH1 activity in neuronal cells may be a novel approach to attenuating AD development. (C) 2014 Elsevier Inc. All rights reserved.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-05
Cheng, Jinbo
Liao, Yajin
Zhou, Lujun
Peng, Shengyi
Chen, Hong
Yuan, Zengqiang
Liao, Yajin
Zhou, Lujun
Abstract： Type I interferon (IFN-I) is critical for a host against viral and bacterial infections via induction of hundreds of interferon-stimulated genes (ISGs), but the mechanism underlying the regulation of IFN-I remains largely unknown. In this study, we first demonstrate that ISG expression is required for optimal IFN-beta levels, an effect that is further enhanced by endoplasmic reticulum (ER) stress. Furthermore, we identify mitochondrial calcium uniporter protein (MCU) as a mitochondrial antiviral signaling protein (MAVS)-interacting protein that is important for ER stress induction and amplified MAVS signaling activation. In addition, by performing an ectopic expression assay to screen a library of 117 human ISGs for effects on IFN-beta levels, we found that tumor necrosis factor receptor 1 (TNFR1) significantly increases IFN-beta levels independent of ER stress. Altogether, our findings suggest that MCU and TNFR1 are involved in the regulation of RIG-I-like receptors (RLR) signaling.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Neurosciences submitted time 2016-05-12
Abstract： The human LGN and SC consist of distinct layers, but their layer-specific response properties remain poorly understood. In this fMRI study, we characterized visual response properties of the magnocellular (M) and parvocellular (P) layers of the human LGN, as well as at different depths in the SC. Results show that fMRI is capable of resolving layer-specific signals from the LGN and SC. Compared to the P layers of the LGN, the M layers preferred higher temporal frequency, lower spatial frequency stimuli, and their responses saturated at lower contrast. Furthermore, the M layers are colorblind while the P layers showed robust response to both chromatic and achromatic stimuli. Visual responses in the SC were strongest in the superficial voxels, which showed similar spatiotemporal and contrast response properties as the M layers of the LGN, but were sensitive to color and responded strongly to isoluminant color stimulus. Thus, the non-invasive fMRI measures show that the M and P layers of human LGN have similar response properties as that observed in non-human primates and the superficial layers of the human SC prefer transient inputs but are not colorblind. (C) 2015 Elsevier Inc. All rights reserved.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-12
Abstract： Vesicle recycling is pivotal for maintaining reliable synaptic signaling, but its basic properties remain poorly understood. Here, we developed an approach to quantitatively analyze the kinetics of vesicle recycling with exquisite signal and temporal resolution at the calyx of Held synapse. The combination of this electrophysiological approach with electron microscopy revealed that similar to 80% of vesicles (similar to 270,000 out of similar to 330,000) in the nerve terminal are involved in recycling. Under sustained stimulation, recycled vesicles start to be reused in tens of seconds when similar to 47% of the preserved vesicles in the recycling pool (RP) are depleted. The heterogeneity of vesicle recycling as well as two kinetic components of RP depletion revealed the existence of a replenishable pool of vesicles before the priming stage and led to a realistic kinetic model that assesses the size of the subpools of the RP. Thus, our study quantified the kinetics of vesicle recycling and kinetically dissected the whole vesicle pool in the calyceal terminal into the readily releasable pool (similar to 0.6%), the readily priming pool (similar to 46%), the premature pool (similar to 33%), and the resting pool (similar to 20%).
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Neurosciences submitted time 2016-05-12
Guo, Chao
Du, Yifei
Yuan, Deliang
Li, Meixia
Gong, Haiyun
Gong, Zhefeng
Liu, Li
Guo, Chao
Du, Yifei
Yuan, Deliang
Liu, Li
Abstract： Orientation, the spatial organization of animal behavior, is an essential faculty of animals. Bacteria and lower animals such as insects exhibit taxis, innate orientation behavior, directly toward or away from a directional cue. Organisms can also orient themselves at a specific angle relative to the cues. In this study, using Drosophila as a model system, we established a visual orientation conditioning paradigm based on a flight simulator in which a stationary flying fly could control the rotation of a visual object. By coupling aversive heat shocks to a fly's orientation toward one side of the visual object, we found that the fly could be conditioned to orientate toward the left or right side of the frontal visual object and retain this conditioned visual orientation. The lower and upper visual fields have different roles in conditioned visual orientation. Transfer experiments showed that conditioned visual orientation could generalize between visual targets of different sizes, compactness, or vertical positions, but not of contour orientation. Rut-Type I adenylyl cyclase and Dnc-phosphodiesterase were dispensable for visual orientation conditioning. Normal activity and scb signaling in R3/R4d neurons of the ellipsoid body were required for visual orientation conditioning. Our studies established a visual orientation conditioning paradigm and examined the behavioral properties and neural circuitry of visual orientation, an important component of the insect's spatial navigation.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Neurosciences submitted time 2016-05-11
Dai, Jinye
Chen, Peihua
Tian, Hao
Sun, Jianyuan
Dai, Jinye
Tian, Hao
Sun, Jianyuan
Chen, Peihua
Sun, Jianyuan
Abstract： It is well known that voltage-gated calcium channels (VGCCs)-mediated Ca2+ influx triggers evoked synaptic vesicle release. However, the mechanisms of Ca2+ regulation of spontaneous miniature vesicle release (mini) remain poorly understood. Here we show that blocking VGCCs at the juvenile mice (C57BL/6) calyx of Held synapse failed to cause an immediate change in minis. Instead, it resulted in a significant reduction (similar to 40%) of mini frequency several minutes after the blockage. By recording VGCC activity and single vesicle fusion events directly at the presynaptic terminal, we found that minis did not couple to VGCC-mediated Ca2+ entry, arguing for a lack of direct correlation between mini and transient Ca2+ influx. Moreover, mini frequencies displayed a lower apparent Ca2+ cooperativity than those of evoked release. In agreement with this observation, abrogation of the Ca2+ sensor synaptotagmin-2 had no effect on apparent Ca2+ cooperativity of minis. Together, our study provides the first direct evidence that spontaneous minis are not mediated by transient Ca2+ signals through VGCCs and are triggered by a Ca2+-sensing mechanism that is different from the evoked release at these microdomain VGCC-vesicle coupled synapses.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Developmental Biology submitted time 2016-05-05
Abstract： microRNA-9 (miR-9) is highly expressed in the nervous system across species and plays essential roles in neurogenesis and axon growth; however, little is known about the mechanisms that link miR-9 with dendrite growth. Using an in vivo model of Drosophila class I dendrite arborization (da) neurons, we show that miR-9a, a Drosophila homolog of mammalian miR-9, downregulates the cadherin protein Flamingo (Fmi) thereby attenuating dendrite development in a non-cell autonomous manner. In miR-9a knockout mutants, the dendrite length of a sensory neuron ddaE was significantly increased. Intriguingly, miR-9a is specifically expressed in epithelial cells but not in neurons, thus the expression of epithelial but not neuronal Fmi is greatly elevated in miR-9a mutants. In contrast, overexpression of Fmi in the neuron resulted in a reduction in dendrite growth, suggesting that neuronal Fmi plays a suppressive role in dendrite growth, and that increased epithelial Fmi might promote dendrite growth by competitively binding to neuronal Fmi. Fmi has been proposed as a G protein-coupled receptor (GPCR), we find that neuronal G protein Gq (Gq), but not Go, may function downstream of Fmi to negatively regulate dendrite growth. Taken together, our results reveal a novel function of miR-9a in dendrite morphogenesis. Moreover, we suggest that Gq might mediate the intercellular signal of Fmi in neurons to suppress dendrite growth. Our findings provide novel insights into the complex regulatory mechanisms of microRNAs in dendrite development, and further reveal the interplay between the different components of Fmi, functioning in cadherin adhesion and GPCR signalling. (c) 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 225-237, 2016
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Neurosciences submitted time 2016-05-12
Abstract： The brain constantly creates perceptual predictions about forthcoming stimuli to guide perception efficiently. Abundant studies have demonstrated that perceptual predictions modulate sensory activities depending on whether the actual inputs are consistent with one particular prediction. In real-life contexts, however, multiple and even conflicting predictions might concurrently exist to be tested, requiring a multiprediction coordination process. It remains largely unknown how multiple hypotheses are conveyed and harmonized to guide moment-by-moment perception. Based on recent findings revealing that multiple locations are sampled alternatively in various phase of attentional rhythms, we hypothesize that this oscillation-based temporal organization mechanism may also underlie the multiprediction coordination process. To address the issue, we used well established priming paradigms in combination with a time-resolved behavioral approach to investigate the fine temporal dynamics of the multiprediction harmonization course in human subjects. We first replicate classical priming effects in slowly developing trends of priming time courses. Second, after removing the typical priming patterns, we reveal a new theta-band (similar to 4 Hz) oscillatory component in the priming behavioral data regardless of whether the prime was masked. Third, we show that these theta-band priming oscillations triggered by congruent and incongruent primes are in an out-of-phase relationship. These findings suggest that perceptual predictions return to low-sensory areas not continuously but recurrently in a theta-band rhythm (every 200-300 ms) and that multiple predictions are dynamically coordinated in time by being conveyed in different phases of the theta-band oscillations to achieve dissociated but temporally organized neural representations.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-12
Abstract： Tandem-arranged PDZ [PSD-95 (postsynaptic density-95), Dlg (discs large homologue) and ZO-1 (zonula occludens-1)] domains often form structural and functional supramodules with distinct target-binding properties. In the present study, we found that the two PDZ domains within the PDZ34 tandem of Scribble, a cell polarity regulator, tightly pack in a 'front-to-back' mode to form a compact supramodule. Although PDZ4 contains a distorted alpha B/beta B pocket, the attachment of PDZ4 to PDZ3 generates an unexpected interdomain pocket that is adjacent to and integrates with the canonical aB/aB pocket of PDZ3 to form an expanded target-binding groove. The structure of the PDZ34-target peptide complex further demonstrated that the peptide binds to this expanded target-binding groove with its upstream residues anchoring into the interdomain pocket directly. Mutations of the interdomain pocket and disruptions of the PDZ34 supramodule both interfere with its target-binding capacity. Therefore, the interdomain interface between the PDZ34 supramodule is intrinsically required for its target recognition and determines its target-binding specificity. This interdomain interface-mediated specific recognition may represent a novel mode of target recognition and would broaden the target-binding versatility for PDZ supramodules. The supramodular nature and target recognitionmode of the PDZ34 tandem found in the present study would also help to identify the new binding partners of Scribble and thus may direct further research on the PDZ domain-mediated assembly of Scribble polarity complexes.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-11
Abstract： Chromodomain helicase DNA-binding protein 2 (CHD2) has been associated with a broad spectrum of neurodevelopmental disorders, such as autism spectrum disorders and intellectual disability. However, it is largely unknown whether and how CHD2 is involved in brain development. Here, we demonstrate that CHD2 is predominantly expressed in Pax6(+) radial glial cells (RGs) but rarely expressed in Tbr2(+) intermediate progenitors (IPs). Importantly, the suppression of CHD2 expression inhibits the self-renewal of RGs and increases the generation of IPs and the production of neurons. CHD2 mediates these functions by directly binding to the genomic region of repressor element 1-silencing transcription factor (REST), thereby regulating the expression of REST. Furthermore, the overexpression of REST rescues the defect in neurogenesis caused by CHD2 knockdown. Taken together, these findings demonstrate an essential role of CHD2 in the maintenance of the RGs self-renewal levels, the subsequent generation of IPs, and neuronal output during neurogenesis in cerebral cortical development, suggesting that inactivation of CHD2 during neurogenesis might contribute to abnormal neurodevelopment. Stem Cells2015;33:1794-1806
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Neurosciences submitted time 2016-05-11
Wen, Bo
Qian, Hao
Feng, Jing
Ge, Rong-Jing
Wang, Jin-Hui
Wen, Bo
Qian, Hao
Wang, Jin-Hui
Ge, Rong-Jing
Xu, Xin
Cui, Zhi-Qiang
Zhu, Ru-Yuan
Pan, Long-Sheng
Lin, Zhi-Pei
Abstract： Main ProblemEpilepsy is one of the more common neurological disorders. The medication is often ineffective to the patients suffering from intractable temporal lobe epilepsy (TLE). As their seizures are usually self-terminated, the elucidation of the mechanism underlying endogenous seizure termination will help to find a new strategy for epilepsy treatment. We aim to examine the role of inhibitory interneurons in endogenous seizure termination in TLE patients. MethodsWhole-cell recordings were conducted on inhibitory interneurons in seizure-onset cortices of intractable TLE patients and the temporal lobe cortices of nonseizure individuals. The intrinsic property of the inhibitory interneurons and the strength of their GABAergic synaptic outputs were measured. The quantitative data were introduced into the computer-simulated neuronal networks to figure out a role of these inhibitory units in the seizure termination. ResultsIn addition to functional downregulation, a portion of inhibitory interneurons in seizure-onset cortices were upregulated in encoding the spikes and controlling their postsynaptic neurons. A patch-like upregulation of inhibitory neurons in the local network facilitated seizure termination. The upregulations of both inhibitory neurons and their output synapses synergistically shortened seizure duration, attenuated seizure strength, and terminated seizure propagation. ConclusionAutomatic seizure termination is likely due to the fact that a portion of the inhibitory neurons and synapses are upregulated in the seizure-onset cortices. This mechanism may create novel therapeutic strategies to treat intractable epilepsy, such as the simultaneous upregulation of cortical inhibitory neurons and their output synapses.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics >> Biochemistry & Molecular Biology submitted time 2016-05-11
Abstract： Age-related memory impairment (AMI) is a phenomenon observed from invertebrates to human. Memory extinction is proposed to be an active inhibitory modification of memory, however, whether extinction is affected in aging animals remains to be elucidated. Employing a modified paradigm for studying memory extinction in fruit flies, we found that only the stable, but not the labile memory component was suppressed by extinction, thus effectively resulting in higher memory loss in aging flies. Strikingly, young flies were able to fully restore the stable memory component 3 h post extinction, while aging flies failed to do so. In conclusion, our findings reveal that both accelerated extinction and impaired restoration contribute to memory impairment in aging animals. (C) 2015 Elsevier Inc. All rights reserved.
Peer Review Status:Awaiting Review
Subjects: Biology >> Biophysics submitted time 2016-05-05
Abstract： Secreted Wnts play diverse roles in a non-cell-autonomous fashion. However, the cell-autonomous effect of unsecreted Wnts remains unknown. Endoplasmic reticulum (ER) stress is observed in specialized secretory cells and participates in pathophysiological processes. The correlation between Wnt secretion and ER stress remains poorly understood. Here, we demonstrated that Drosophila miR-307a initiates ER stress specifically in wingless (wg)-expressing cells through targeting wntless (wls/evi). This phenotype could be mimicked by retromer loss-of-function or porcupine (porc) depletion, and rescued by wg knockdown, arguing that unsecreted Wg triggers ER stress. Consistently, we found that disrupting the secretion of human Wnt5a also induced ER stress in mammalian cells. Furthermore, we showed that a C-terminal KKVY-motif of Wg is required for its retrograde Golgi-to-ER transport, thus inducing ER stress. Next, we investigated if COPI, the regulator of retrograde transport, is responsible for unsecreted Wg to induce ER stress. To our surprise, we found that COPI acts as a novel regulator of Wg secretion. Taken together, this study reveals a previously unknown Golgi-to-ER retrograde route of Wg, and elucidates a correlation between Wnt secretion and ER stress during development.
Peer Review Status:Awaiting Review
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