Biology subjects

Saito, K.

Publications and source records attributed to Saito, K..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

Active fluctuations of cytoplasmic actomyosin networks facilitate dynein-driven intracellular transport along microtubules

Inside cells, molecular motors transport cargoes within the actively fluctuating environment known as the cytoplasm. How fluctuations in the cytoplasm affect motor-driven transport is not fully understood. In this study, we investigated the role of fluctuations for transport along microtubules using C. elegans early embryos, focusing on transport driven by cytoplasmic dynein. An artificial motor-cargo complex showed faster transport in vivo than in vitro, suggesting an in vivo acceleration mechanism. We also found that endogenous early endosome transport by dynein is significantly enhanced by the fluctuations in the cytoplasm, which is attributed to the activity of actomyosin networks. An in vitro force measurement of dynein suggests that the asymmetric force response would play a key role in the acceleration. This study provides insights into a regulatory mechanism of molecular motors within actively fluctuating cytoplasm, potentially utilizing random force originating from fluctuating dynamics in the cytoplasm to increase transport efficiency.

biophysics↗

bioRxiv2024

Cell-type-specific fluorescent tagging of endogenous target proteins reveals synaptic enrichment and dynamic regulations of dopamine receptors

Dopamine can play opposing physiological roles depending on the receptor subtype. In the fruit fly Drosophila melanogaster, Dop1R1 and Dop2R encode the D1- and D2-like receptors, respectively, and are reported to oppositely regulate intracellular cAMP levels. Here, we profiled the expression and subcellular localization of endogenous Dop1R1 and Dop2R in specific cell types in the mushroom body circuit. For cell-type-specific visualization of endogenous proteins, we employed reconstitution of split-GFP tagged to the receptor proteins. We detected dopamine receptors at both presynaptic and postsynaptic sites in multiple cell types. Quantitative analysis revealed enrichment of both receptors at the presynaptic sites, with Dop2R showing a greater degree of localization than Dop1R1. The presynaptic localization of Dop1R1 and Dop2R in dopamine neurons suggests dual feedback regulation as autoreceptors. Furthermore, we discovered a starvation-dependent, bidirectional modulation of the presynaptic receptor expression in the PAM and PPL1 clusters, two distinct subsets of dopamine neurons, suggesting regulation of appetitive behaviors. Our results highlight the significance of the co-expression of the two opposing dopamine receptors in the spatial and conditional regulation of dopamine responses in neurons.

neuroscience↗

bioRxiv2024

A Novel Method to Visualize Active Small GTPases Unveils Distinct Sites of Sar1 Activation During Collagen Secretion.

Small GTPases are essential in various cellular signaling pathways, and detecting their activation within living cells is crucial for understanding cellular processes. Fluorescence resonance energy transfer is widely used to study the interaction between activated small GTPases and their effectors, but it is limited to those with well-defined effectors, excluding Sar1. Here, we present a novel method, SAIYAN (Small GTPase ActIvitY ANalyzing), for detecting the activation of endogenous small GTPases via fluorescent signals utilizing a split mNeonGreen system. We demonstrated Sar1 activation at the endoplasmic reticulum (ER) exit site and successfully detected its activation state in various cellular conditions. Utilizing the SAIYAN system in collagen-secreting cells, we discovered activated Sar1 localized both at ER exit sites and ER-Golgi intermediate compartment (ERGIC) regions. Additionally, impaired collagen secretion led to the confinement of activated Sar1 at the ER exit sites, underscoring the significance of Sar1 activation through the ERGIC in collagen secretion.

cell biology↗

bioRxiv2024

Osiris gene family defines the cuticle nano-patterns of Drosophila

Nanostructures of pores and protrusions in the insect cuticle modify molecular permeability and surface wetting and help insects sense a variety of environmental cues. The cellular mechanism specifying cuticle nanostructures is poorly understood. Here, we show that insect-specific Osiris family genes are expressed in various cuticle-secreting cells in the Drosophila head in the early stage of cuticle secretion and collectively cover nearly the entire surface of the head epidermis. We show that each sense organ cell with various cuticular nanostructures expresses a unique combination of Osiris genes. Osiris gene mutations caused various cuticle defects in the corneal nipples of the eye and pores of the chemosensory sensilla. Osiris genes provide an entry point for investigating cuticle nanopatterning in insects.

developmental biology↗

bioRxiv2023

The effects of paroxetine-induced transient apoptosis and brain remodeling on social behavior in developing zebrafish

Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by various genetic and environmental factors. This disorder has the cardinal symptoms including impaired social behavior involving the amygdala. Ingesting antidepressants such as paroxetine in early pregnancy increases the risk of ASD in offspring. However, a comprehensive picture of the underlying pathogenic mechanisms remains elusive. Here we demonstrate that early exposure of zebrafish embryos to paroxetine retards neurogenesis in the optic tectum and the telencephalon that includes a region corresponding to the mammalian amygdala. Paroxetine-treated embryos exhibit impaired growth, with small heads and short body lengths resulting from transient apoptosis. This is reminiscent of the early-onset fetal growth restriction (FGR) associated with ASD. Interestingly, the delayed neurogenesis in the small heads was found to be restored after the cessation of paroxetine. This restoration was accompanied by extended retinotectal projections, suggesting brain-preferential remodeling. Finally, social behavior of the paroxetine-treated fish was examined. Our findings imply a biological mechanism underlying early exposure to paroxetine, a risk factor associated with the pathogenesis of ASD.

pharmacology and toxicology↗

bioRxiv2023

Maternal sterol 27-hydroxylase is crucial for securing fetal development

The maternal body helps in providing nutrients and degrading toxic metabolites instead of the fetal body; disruptions in these mechanisms affect normal fetal development. Sterol 27-hydroxylase (Cyp27a1) is involved in the alternative pathway of bile acid synthesis, which is enhanced during pregnancy. However, its role in fetal development remains unclear. Here, we demonstrate that maternal Cyp27a1 activity is essential for progression of normal pregnancy and fetal organ formation. Depletion of maternal Cyp27a1 reduced the pregnancy rate and litter size. Newborn mice died of respiratory distress syndrome resulting from the absence of mature alveolar epithelial cells. These phenotypes were caused by 7-hydroxycholesterol (7-HC) accumulating in Cyp27a1-deficient mice. Mechanistically, 7-HC destabilized the Fau protein, mediating ribosome assembly, the downregulation of which caused poor polysome formation, lower protein synthesis, and impaired lung maturation. Overall, this study revealed an essential mechanism of securing fetal development by degrading a toxic metabolite in the maternal body.

developmental biology↗

bioRxiv2023

Lipopolysaccharides derived from Porphyromonas gingivalis and Escherichia coli: differential and interactive effects on novelty-induced hyperlocomotion, blood cytokine levels and TRL4-related processes

Lipopolysaccharide (LPS), a component of the Gram-negative bacterial cell wall, activates Toll-like receptors (TLRs). Porphyromonas gingivalis (Pg) may be involved in the progression of periodontal disease. Mice exposed to a novel environment show hyperlocomotion that is inhibited by systemic administration of LPS derived from Escherichia coli (Ec-LPS). However, whether Pg-LPS influences novelty-induced locomotion is unknown. Accordingly, we carried out an open field test to analyse the effects of Pg-LPS. For comparison, effects of Ec-LPS were also studied. We also investigated the influence of systemic administration of Pg-LPS or Ec-LPS on IL-6, TNF-alpha, and IL-10 levels in blood, as they could be involved in the changes in locomotion. The TLR4 receptor antagonist TAK-242 was used to study the involvement of TLR4. Since Pg-LPS may block TLR4 in vitro, we analysed the effects of Pg-LPS on Ec-LPS-induced changes in behavioural and biochemical parameters. Male ddY mice were used. Compounds were administered intraperitoneally. Ec-LPS (840 {micro}g/kg), but not Pg-LPS (100, 500 and 840 {micro}g/kg), inhibited novelty-induced locomotion, which was reversed by TAK-242 (3.0 mg/kg). Ec-LPS (840 {micro}g/kg) increased blood levels of IL-6 and IL-10, which was antagonized by TAK-242 (3.0 mg/kg). However, TAK-242 did not inhibit Ec-LPS-induced increases in TNF-alpha levels in blood. Pg-LPS (100, 500, and 840 {micro}g/kg) did not alter blood IL-6, TNF-alpha, or IL-10 levels. The Ec-LPS-induced increase in blood IL-10, but not IL-6 and TNF-alpha, levels was inhibited by Pg-LPS (500 {micro}g/kg). These results suggest that TLR4 stimulation mediates the inhibition of novel environment-induced locomotion in mice following systemic administration of Ec-LPS, while also increasing blood IL-6 and IL-10 levels. In contrast, Pg-LPS did not exhibit these effects. The present study also provides in vivo evidence that Pg-LPS can inhibit TLR4-mediated increases in blood IL-10 levels, which is thought to prevent the development of periodontal disease.

microbiology↗

bioRxiv2023

TEM Experiment and Complete Genome Sequencing with Comparative Genomic Analysis to Uncover Potential Probiotic Features of Isolated Lactobacillus delbrueckii subsp. indicus TY-11

BackgroundProbiotics refer to living microorganisms that exerts a variety of beneficial effects on human health. On the contrary, they also can cause infection, produce toxins within the body, and transfer antibiotic resistant genes to the other microorganisms in the digestive tract necessitating a comprehensive safety assessment. This study aimed to conduct functional genomic analysis to uncover the probiotic potential of Lactobacillus delbrueckii subsp. indicus TY-11 isolated from native yogurt in Bangladesh. We also performed Transmission Electron Microscopic (TEM) analysis, comparative genomic study as well as phylogenetic tree construction with 332 core genes from 262 genomes. These experiments on subspecies indicus were not studied previously. ResultsThe strain TY-11 was identified as Lactobacillus delbrueckii subsp. indicus, whose genome (1916674bp) contained genes to adapt to diverse and stressful environments of the human gut, and no gene was identified for either antibiotic resistance or toxic metabolites. It embraced genes for the degradation of toxic metabolites, treatment of lactose intolerance, toll-like receptor 2-dependent innate immune response, heat and cold shock, bile salts tolerance in the gut, and acidic pH tolerance in the stomach. Genes were annotated for inhibiting pathogenic bacteria in the gut by inhibitory substances, (bacteriocin: Helveticin-J (331bp) and Enterolysin-A (275bp), hydrogen peroxide, and acid); blockage of adhesion sites; and competition for nutrients. Its metabolic pathway helped the human gut to recover the digestive disorders and digest indigestible nutrients. The TY-11 genome possessed additional 37 core genes of subspecies indicus which were deficient in the core genome of the most popular subspecies bularicus. ConclusionsThis is the first study to explore the molecular insights into intestinal residence and probiotic roles including antimicrobial activities of a representative strain (TY-11) of Lactobacillus delbrueckii subsp. indicus.

genomics↗

bioRxiv2023

Mettl1-dependent m7G tRNA modification is essential for maintaining spermatogenesis and fertility in Drosophila melanogaster

N7-methylguanosine (m7G) in the variable loop region of tRNA is catalyzed by METTL1/WDR4 heterodimer and stabilizes target tRNA. Here, we reveal essential functions of Mettl1 in Drosophila fertility. Knockout of Mettl1 (Mettl1-KO) lost the elongated spermatids and mature sperm, which was fully rescued by a Mettl1-transgene expression, but not a catalytic-dead Mettl1 transgene. This demonstrates that Mettl1-dependent m7G is required for spermatogenesis. Mettl1-KO resulted in a loss of m7G modification on a subset of tRNAs and a decreased level of tRNA expression. Strikingly, overexpression of the translational elongation factor, EF11, which can compete with the rapid tRNA decay (RTD) pathway in S. cerevisiae, significantly counteracted the sterility of Mettl1-KO males, supporting a critical role of m7G modification of tRNAs in spermatogenesis. Ribosome profiling showed that Mettl1-KO led to the ribosome stalling at codons decoded by tRNAs that were reduced in expression. Mettl1-KO also significantly reduced the translation efficiency of genes involved in elongated spermatid formation and sperm stability. These findings reveal a developmental role for m7G tRNA modifications and indicate that m7G modification-dependent tRNA stability differs among tissues.

molecular biology↗

bioRxiv2023

Developmental noise and phenotypic plasticity are correlated in Drosophila simulans

Non-genetic variation is the phenotypic variation induced by the differential expression of a genotype in response to varying environmental cues and is broadly categorized into two types: phenotypic plasticity and developmental noise. These variation aspects have been suggested to play an important role in adaptive evolution; however, the mechanisms by which these two types of non-genetic variations influence the evolutionary process are currently poorly understood. Using a machine-learning based phenotyping tool, we independently quantified the phenotypic plasticity and developmental noise in the wing morphological traits of a fruit fly Drosophila simulans. Utilizing a rearing experiment, we demonstrated plastic responses in both wing size and shape as well as non-zero heritability of both phenotypic plasticity and developmental noise, which suggests that adaptive phenotypic plasticity can evolve via genetic accommodation in the wing morphology of D. simulans. We found a positive correlation between phenotypic plasticity and developmental noise, while the correlation between the plastic response to three kinds of environmental factors that were examined (nutrient condition, temperature, and light-dark cycle) were poor. These results suggest that phenotypic plasticity and developmental noise contribute to evolvability in a similar manner, however, the mechanisms that underlie the correspondence between these two variation types remains to be elucidated. Lay SummaryNon-genetic variations consist of phenotypic plasticity and developmental noise, and these variations have been suggested to influence the direction and the rate of evolution. However, the role of phenotypic plasticity and developmental noise in evolutionary process is still poorly understood. Using a rearing experiment, we examined the heritability of plasticity and developmental noise, the correlation of the strength of plastic response to three kinds of environmental factors, and the relationship between plasticity and developmental noise in wing size and wing shape in Drosophila simulans. We found that the degree of phenotypic plasticity and developmental noise were heritable, and positively correlated with each other. Our results suggest that there two non-genetic variations dependently affect the direction and the rate of evolution together.

evolutionary biology↗

bioRxiv2023

Absence of electron transfer-associated changes in the time-dependent X-ray free-electron laser structures of the photosynthetic reaction center

Using the X-ray free-electron laser (XFEL) structures of the photosynthetic reaction center from Blastochloris viridis that show light-induced time-dependent structural changes [Dods, R.et al. (2021) Nature 589, 310-314], we investigated time-dependent changes in the energetics of the electron transfer pathway, considering the entire protein environment of the protein structures and titrating the redox active sites in the presence of all fully equilibrated titratable residues. In the dark and charge-separation intermediate structures, the calculated redox potential (Em) values for the accessory bacteriochlorophyll and bacteriopheophytin in the electron-transfer active branch (BL and HL) are higher than those in the electron-transfer inactive branch (BM and HM). However, the stabilization of the [PLPM]*+HL*- state owing to protein reorganization is not clearly observed in the Em(HL) values in the charge-separated 5-ps ([PLPM]*+HL*- state) structure. Furthermore, the expected chlorin ring deformation upon formation of HL*-(saddling mode) is absent in the HL geometry of the original 5-ps structure. These findings suggest that there is no clear link between the time-dependent structural changes and the electron transfer events in the XFEL structures.

biophysics↗

bioRxiv2023

Characterization of Tryptophan Oxidation Affecting D1 Degradation by FtsH in the Photosystem II Quality Control of Chloroplasts

Photosynthesis is one of the most important reactions for sustaining our environment. Photosystem II (PSII) is the initial site of photosynthetic electron transfer by water oxidation. Light in excess, however, causes the simultaneous production of reactive oxygen species (ROS), leading to photo-oxidative damage in PSII. To maintain photosynthetic activity, the PSII reaction center protein D1, which is the primary target of unavoidable photo-oxidative damage, is efficiently degraded by FtsH protease. In PSII subunits, photo-oxidative modifications of several amino acids such as Trp have been indeed documented, whereas the linkage between such modifications and D1 degradation remains elusive. Here, we show that an oxidative post-translational modification of Trp residue at the N-terminal tail of D1 is correlated with D1 degradation by FtsH during high-light stress. We revealed that Arabidopsis mutant lacking FtsH2 had increased levels of oxidative Trp residues in D1, among which an N-terminal Trp-14 was distinctively localized in the stromal side. Further characterization of Trp-14 using chloroplast transformation in Chlamydomonas indicated that substitution of D1 Trp-14 to Phe, mimicking Trp oxidation enhanced FtsH-mediated D1 degradation under high light, although the substitution did not affect protein stability and PSII activity. Molecular dynamics simulation of PSII implies that both Trp-14 oxidation and Phe substitution cause fluctuation of D1 N-terminal tail. Furthermore, Trp-14 to Phe modification appeared to have an additive effect in the interaction between FtsH and PSII core in vivo. Together, our results suggest that the Trp oxidation at its N-terminus of D1 may be one of the key oxidations in the PSII repair, leading to processive degradation by FtsH. Competing Interest StatementThe authors have no conflict of interest, financial or otherwise, in relation to this study Impact StatementOxidative modification of Tryptophan residues in the reaction center protein D1 may be a key to drive the Photosystem II repair, likely enhancing accessibility of FtsH protease to D1.

plant biology↗

bioRxiv2023

A novel mouse allele of the DNA/RNA helicase senataxin (Setxspcar3) causing meiotic arrest of spermatocytes and male infertility

An unbiased screen for discovering novel genes for fertility identified the spcar3, spermatocyte arrest 3, mutant phenotype. The spcar3 mutation identified a new allele of the Setx gene, encoding senataxin, a DNA/RNA helicase that regulates transcription termination by resolving DNA/RNA hybrid R-loop structures. Although mutations in the human SETX gene cause neural disorders, Setxspcar3 mutant mice do not show any apparent neural phenotype, but instead exhibit male infertility and female subfertility. Histology of the Setxspcar3mutant testes revealed absence of spermatids and mature spermatozoa in the seminiferous tubules. Cytological analysis of chromosome spread preparations of the Setxspcar3 mutant spermatocytes revealed normal synapsis, but aberrant DNA damage in the autosomes, and defective formation of the sex body. Furthermore, Setxspcar3 testicular cells exhibited abnormal accumulation of R-loops compared to wild type testicular cells. Transient expression assays identified regions of the senataxin protein required for sub-nuclear localization. Together, these results not only confirm that senataxin is required for normal meiosis and spermatogenesis but also provide a new resource for determination of its role in maintaining R-loop formation and genome integrity.

cell biology↗

bioRxiv2022

A jasmonate-responsive ERF transcription factor regulates steroidal glycoalkaloid biosynthesis genes in eggplant

Steroidal glycoalkaloids (SGAs) are a class of cholesterol-derived anti-nutritional defense compounds that are produced in species of the genus Solanum, such as tomato (S. lycopersicum), potato (S. tuberosum), and eggplant (S. melongena). However, the regulation of defense-related metabolites in eggplant remains underexplored. In tomato and potato, the JASMONATE-RESPONSIVE ETHYLENE RESPONSE FACTOR 4 (JRE4) transcription factor positively regulates a large number of genes involved in SGA biosynthesis. Here, we report that overexpression of eggplant JRE4 (SmJRE4) induces numerous metabolic genes involved in SGA biosynthesis in leaves. We demonstrate jasmonate-dependent induction of SmJRE4 and its downstream metabolic genes and show that ethylene treatment attenuates this induction. Our findings thus provide molecular insights into SGA biosynthesis and its regulation in this major crop.

plant biology↗

bioRxiv2022

Sox17 downstream gene Rasip1 is involved in the hematopoietic activity of intra-aortic hematopoietic clusters in the midgestation mouse embryo

BackgroundDuring mouse embryonic development, definitive hematopoiesis is first detected around embryonic day (E) 10.5 in the aorta-gonad-mesonephros (AGM) region. Hematopoietic stem cells (HSCs) arise in the dorsal aortas intra-aortic hematopoietic cell clusters (IAHCs). We have previously reported that a transcription factor Sox17, is expressed in IAHCs, and that, among them, CD45lowc-Kithigh cells have high hematopoietic activity. Furthermore, forced expression of Sox17 in this population of cells can maintain the formation of hematopoietic cell clusters. However, how Sox17 does so, particularly downstream signaling involved, remains poorly understood. The purpose of this study is to search for new Sox17 targets which contribute to cluster formation with hematopoietic activity. MethodsRNA-sequencing (RNA-seq) analysis was done to identify genes that are up- regulated in Sox17-expressing IAHCs as compared with Sox17-negative ones. Among the top 7 highly expressed genes, Rasip1 which had been reported to be a vascular-specific regulator was focused on in this study and firstly the whole-mount immunostaining was done. We conducted a luciferase reporter assay to identify the Sox17 binding site for Rasip1 gene induction. We also analyzed the cluster formation and the multi-lineage colony forming ability of Rasip1-transduced cells and Rasip1-knockdown Sox17-transduced cells. ResultsThe increase of the Rasip1 expression level was observed in Sox17-positive CD45lowc-Kithigh cells as compared with the Sox17-nonexpressing control. Also, the expression level of the Rasip1 gene was increased by the Sox17-nuclear translocation. Rasip1 was expressed on the membrane of IAHCs, overlapping with the endothelial cell marker, CD31, and hematopoietic stem/progenitor marker (HSPC), c-Kit. Overexpression of Rasip1 in CD45lowc-Kithigh cells led to a significant but transient increase in hematopoietic activity, while Rasip1 knock-down in Sox17-transduced cells decreased the cluster formation and diminished the colony-forming ability. ConclusionsRasip1 knockdown in Sox17-transduced CD45lowc-Kithigh cells displayed a significant decrease in the multi-lineage colony forming ability and the cluster size. Rasip1 overexpression in Sox17-untransduced CD45lowc-Kithigh cells led to a significant but transient increase in the multi-lineage colony forming ability, suggesting the presence of a cooperating factor for sustained hematopoietic activity.

developmental biology↗

bioRxiv2022

Imbalance of circuit plasticity and consolidation in autism model marmosets is adjusted by oxytocin administration

Alterations in the experience-dependent and autonomous elaboration of neural circuits are assumed to underlie autism spectrum disorder (ASD), though it is unclear what synaptic traits are responsible. Here, we used a valproic acid-induced ASD marmoset model, which shares common molecular features with idiopathic ASD, to investigate the structural dynamics of tuft dendrites of upper-layer pyramidal neurons and adjacent axons in the dorsomedial prefrontal cortex using two-photon microscopy. In model marmosets, dendritic spine turnover was upregulated, and spines were actively generated in clusters and subsequently survived more often than in control marmosets. Presynaptic boutons in local axons but not in commissural long-range axons showed hyperdynamic turnover in model marmosets, suggesting alterations in projection-specific plasticity. Intriguingly, nasal administration of oxytocin reduced the clustered spine emergence. Enhanced clustered spine generation, possibly unique to certain presynaptic partners, may be associated with ASD and may be a potential therapeutic target.

neuroscience↗

bioRxiv2022

High salt induces cognitive impairment via the angiotensin II-AT1 and prostaglandin E2-EP1 systems

High salt (HS) intake is a known risk factor for hypertension and dementia. Clinical studies have shown that antihypertensive drugs can decrease the incidence of dementia. Accordingly, a strong relationship can be suggested between hypertension and cognitive impairment. It is well-known that angiotensin II (Ang II)-AT1 and prostaglandin E2 (PGE2)-EP1 systems are involved in hypertension and neurotoxicity. However, the involvement of these systems in HS-mediated hypertension and emotional and cognitive impairments remains unclear. Herein, we demonstrated that hypertension and impaired social behavior and object recognition memory following HS intake could be associated with tau hyperphosphorylation, decreased phosphorylation of Ca2+/calmodulin-dependent protein kinase II (CaMKII), and postsynaptic density protein 95 (PSD95) expression in the prefrontal cortex and hippocampus of mice. These changes were blocked by pharmacological treatment with losartan, an Ang II receptor blocker (ARB), or EP1 gene knockout. Our findings suggest that Ang II-AT1 and PGE2-EP1 systems could be novel therapeutic targets for hypertension-induced dementia.

neuroscience↗

bioRxiv2022

Hypomorphism of a novel long ERα isoform causes severe reproductive dysfunctions in female mice

Estrogen receptor alpha (ER)-mediated estrogen signaling play a pivotal role in both reproductive and non-reproductive functions. Transcriptional regulation of ER gene is highly complex, with multiple transcript variants being differentially produced across the tissues. However, tissue-specific variation and physiological specificity of the ER variants are not yet fully understood. In an attempt to generate a Cre-dependently restorable ER-null mice for functional investigation of the genetic sufficiency, we unexpectedly produced ER hypomorphic mice with biased downregulation of a previously unappreciated long ER isoform that is enriched in the female reproductive organs (uterus and ovaries) and the pituitary but minimally expressed in the brain. Female homozygous mutant mice were capable of pregnancy but displayed irregular estrus cycle and rarely maintained alive newborns without significant morphological and pathological changes in reproductive system and the disruption of body weight homeostasis, indicating the vital role of this long isoform in female reproductive function. Collectively, our results define a tissue-specifically enriched long ER isoform and its preferential role in female reproductive function over body weight homeostasis.

physiology↗