Biology subjects

Zeng, R.

Publications and source records attributed to Zeng, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Shared and distinct immunometabolic states link to divergent pathology in cutaneous mycobacterial infections

Cutaneous mycobacterial infections provide a common tissue setting in which related intracellular pathogens elicit distinct pathological responses, but the innate immune basis of this divergence remains incompletely understood. Here, we combined single-cell profiling from 33 individuals with histological and functional analyses, examining healthy skin and lesions from multibacillary leprosy (MB), paucibacillary leprosy (PB), cutaneous tuberculosis (CTB) and Mycobacterium marinum infection (Mari). All infections showed lower mononuclear phagocyte and higher natural killer (NK) cell proportions within the CD45 compartment, alongside shared and infection-associated dendritic cell, macrophage and NK cell programs. CTB and Mari displayed broader macrophage antimicrobial signatures, whereas MB showed lipid-associated programs and attenuated interferon-associated effector expression across multiple macrophage subsets. Reduced expression of fructose-1,6-bisphosphatase 1 (FBP1) was associated with the absence of Langhans giant cells in MB, and pharmacological FBP1 inhibition nearly abolished fusion of macrophages. Compared with NK cells from Mari, MB NK cells showed reduced central carbon and oxidative metabolism signatures alongside increased lipid-associated programs. Functional experiments showed that inhibition of glucose utilization, disruption of mitochondrial function, or co-culture with foamy macrophages abundant in MB lesions reduced NK cell IFN-{gamma} production. These findings identify shared and distinct innate immune programs and suggest that their interplay with local metabolic environments shapes divergent pathology across cutaneous mycobacterial infections.

immunology↗

bioRxiv2026

A tunable aqueous architecture modulates functionaloutput in biomolecular condensates

Biomolecular condensates organize cellular biochemistry, yet the principles governing their internal solvent architectures remain poorly understood. Most current models focus on macromolecular scaffolds while treating the solvent as a passive, spatially uniform background. Here, we introduce Condensate Spatial Topography via Emission Lifetimes (ConSTEL) to map the continuous solvent polarity landscape inside biomolecular condensates. Using PopZ as a model system, we show that the condensate interior contains a persistent, tunable mosaic of aqueous environments whose apparent polarity, reported by Nile Red fluorescence lifetimes, is organized by thermodynamic state and chemical cues. This microphase-separated solvent architecture defines distinct mesoscale rheological regimes, with intermediate aqueous niches supporting fast, confined tracer motion and highly polar or non-polar extremes forming a slower, viscoelastic mesh. We further demonstrate that drug-like small molecules partition non-uniformly across this landscape according to their physicochemical properties, and that exceeding local solubility limits drives "reciprocal sculpting", in which mismatched guests remodel the host solvent architecture. Together, these results highlight internal solvent organization as an active, tunable determinant of condensate material properties, molecular transport, and partitioning, and suggest that predictive models of condensate function and pharmacology would benefit from incorporating the spatial arrangement of solvent environments alongside bulk composition.

biochemistry↗

bioRxiv2026

Quinone reductase 2 reads H3 serotonylation to support neuronal maturation

Histone H3 Gln5 serotonylation (H3Q5ser) is a recently described posttranslational modification1 that plays important roles in guiding transcriptional permissiveness in brain and peripheral systems2-5. H3Q5ser has been implicated in diverse physiological and pathological processes ranging from neural differentiation1 to sensory processing6, circadian rhythmicity7, stress responsivity8, placental gene regulation9, and tumorigenesis10-19. Since H3Q5ser can occur in combination with H3 Lys4 trimethylation (H3K4me3), most mechanistic studies to date have focused on H3Q5sers roles in modulating H3K4me3 reader interactions, where it has been shown to potentiate TAF3/TFIID binding to H3K4me31,20,21 and inhibit the recruitment of K4me3 demethylases21; however, whether H3 serotonylation functions as an autonomous chromatin signaling mark through dedicated reader proteins has remained unknown. Here, using a combination of proteomic-, structural-, molecular-, epigenomic-, and cellular-based approaches, we demonstrate that the Quinone reductase 2 (QR2) enzyme reads H3Q5ser independently of H3K4me3. CRISPR-Cas9-mediated disruption of H3 serotonylation or QR2s binding to the mark in human induced pluripotent stem cell-derived neurons impairs the establishment of neuronal transcriptional programs, alters synaptic connectivity, and disrupts electrophysiological maturation. These findings thus uncover an H3 serotonylation-dependent chromatin signaling axis that is essential for human neurodevelopment.

molecular biology↗

bioRxiv2025

A Mechanical Logic for Bacterial Navigation

Bacterial motility in unconfined liquids is well understood, but many species inhabit crowded, three-dimensional environments where physical constraints shape navigation. Here, we show that the aquatic bacterium Caulobacter crescentus employs backward swimming to overcome confinement, using a force-sensitive mechanism to control directional switching. Using colloidal "{micro}-Traps" to confine single cells within spherical volumes accessible through a narrow aperture, we reveal that cells engage backward motility to enter pores, explore boundaries, and escape confinement. This directional switching is gated by mechanical load: moderate forces on the flagellum promote backward motion, while excessive load suppresses it, preventing futile effort. This tunable, load-sensitive control offers direct evidence for a mechanical logic that governs motility: backward movement is activated when advantageous and disengaged when not. These findings highlight how physical forces influence microbial navigation and adaptation in complex environments.

biophysics↗

bioRxiv2024

Natural killer cell dysfunction drives keloid pathogenesis

Keloids, characterized by excessive scar tissue resulting from abnormal wound healing, are primarily driven by hyperproliferative fibroblasts and overproduction of extracellular matrix. Although human natural killer (NK) cells are known for their role in inhibiting uncontrolled cell growth through cytokines like IFN-{gamma} and TNF-, they also produce amphiregulin (AREG), which paradoxically promotes cell proliferation and survival. The involvement of NK cells in keloid pathogenesis, however, remains largely unexplored. This study uncovers remarkable functional changes in NK cells within both lesional skin and the blood of keloid patients. In the skin, NK cell-produced IFN-{gamma} plays a pivotal role in limiting keloid progression by inducing fibroblast apoptosis and curbing excessive extracellular matrix production, while NK cell-derived AREG actively opposes these protective effects. Notably, TGF-{beta}-driven fibroblasts in keloid lesions further dampen NK cell IFN-{gamma} production, revealing a complex and dynamic cellular interplay. In the bloodstream of keloid patients, a distinct NK cell subset emerges, marked by elevated interferon-stimulated genes (ISGs) and diminished IFN-{gamma} production, which correlates with increased plasma IFN-{beta} levels. This elevated IFN-{beta} serves as a key initiating factor, driving NK cell exhaustion through impaired mitochondrial function and metabolic disruption. These findings highlight a critical mechanism underlying the functional abnormalities of keloid-associated NK cells and emphasize the influence of both local and systemic factors in shaping NK cell responses in keloid pathogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/624588v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@7501f4org.highwire.dtl.DTLVardef@1d34de5org.highwire.dtl.DTLVardef@19f1c47org.highwire.dtl.DTLVardef@f98882_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIn the skin, NK cell-derived IFN-{gamma} is crucial for suppressing keloid fibroblast proliferation and extracellular matrix production. C_LIO_LIAREG from NK cells counteracts the inhibitory effects of IFN-{gamma} on keloid progression. C_LIO_LIIn the blood, elevated IFN-{beta} in keloid patients drives the emergence of ISG+NK cells with reduced IFN-{gamma} production. C_LIO_LIIFN-{beta} induces mitochondrial dysfunction and functional exhaustion in NK cells. C_LI

immunology↗

bioRxiv2024

PEPCy: Photostable fluoromodules for live cell, super-resolution microscopy of surface proteins

We report the evolution and application of two genetically encoded tags that bind the cyanine dyes Cy3 or Cy5 with high specificity and selectivity, in addition to enhancing their photostability. These tags, which we call PEPCy, can be used to target membrane proteins such as G-protein coupled receptors. Due to their orthogonality and high binding-affinity for cognate cyanine dyes, the PEPCy tags can be used for wash-free labeling of cell surface receptors to observe their dynamics at a single molecule level. Together with self-labeling tags, these photostability enhancing proteins against cyanine dyes present a novel, complementary and powerful approach to explore protein dynamics with high spatiotemporal resolution.

biophysics↗

bioRxiv2023

Transcriptional profiling of skin cancer NK cells reveals the elevated glucocorticoid signaling switches their anti-tumor characteristics to a homeostatic feature

Natural killer (NK) cells are potent mediators of anti-tumor immunity, yet their functions are frequently subverted by tumor microenvironment-driven immunosuppression. Here, we dissect the molecular mechanisms underlying NK cell dysfunction in cutaneous malignancies and identify a paradoxical cytokine shift in tumor-associated NK cells-reduced production of IFN-{gamma} and TNF- alongside elevated amphiregulin (AREG), an EGFR ligand linked to tumor progression. Single-cell transcriptomic analysis indicates that this reprogramming correlates with elevated glucocorticoid receptor (GR/NR3C1) pathway activity in tumor-infiltrating NK cells. Functional validation demonstrated that glucocorticoids specifically induce AREG production in NK cells, with tumor-associated prostaglandin E2 (PGE2) augmenting this response. Genetic ablation or pharmacological inhibition of NR3C1 abolished glucocorticoid-driven AREG induction. Moreover, primary GR activation established persistent chromatin accessibility at the AREG locus, sensitizing NK cells to enhanced AREG production upon secondary glucocorticoid exposure. Functionally, AREG counteracts NK cell-mediated tumor apoptosis, while adoptive transfer of AREG-deficient human NK cells significantly suppressed melanoma, cutaneous squamous cell carcinoma (cSCC), and hepatocellular carcinoma growth in NCG mice. These findings establish the GR-AREG axis as a multi-layered therapeutic target for restoring NK cell anti-tumor function. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=199 SRC="FIGDIR/small/557530v3_ufig1.gif" ALT="Figure 1"> View larger version (36K): org.highwire.dtl.DTLVardef@1ef982forg.highwire.dtl.DTLVardef@f036a7org.highwire.dtl.DTLVardef@941abborg.highwire.dtl.DTLVardef@1670d23_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

miRNA-encoded regulatory peptides modulate cadmium tolerance and accumulation in rice

MicroRNAs (miRNAs) are small non-coding RNAs that play a vital role in plant responses to abiotic and biotic stress. Recently, it has been discovered that some primary miRNAs (pri-miRNAs) encode regulatory short peptides called miPEPs. However, the presence of miPEPs in rice, and their functions in response to abiotic stress, particularly stress induced by heavy metals, remain poorly understood. Here, we identified a functional small peptide (miPEP156e) encoded by pri-miR156e that regulates the expression of miR156 and its target SPL genes, thereby affecting miR156-mediated cadmium (Cd) tolerance in rice. Overexpression of miPEP156e led to a reduction in the accumulation of reactive oxygen species (ROS) and Cd in plants under Cd stress, resulting in improved rice Cd tolerance, as observed in miR156-overexpressing lines and seedlings treated with exogenous miPEP156e. In contrast, miPEP156e mutants displayed sensitivity to Cd stress due to the elevated accumulation of ROS and Cd. Transcriptome analysis further revealed that miPEP156e improved rice Cd tolerance by modulating Cd transporter and ROS scavenging genes. Moreover, we identified five novel miPEPs involved in regulating Cd resistance through exogenous treatment of seedlings with synthetic corresponding miPEPs. Our study provides insights into the regulatory mechanism of miPEP156e in rice response to Cd stress and demonstrates the potential of miPEPs as an effective tool for improving crop abiotic stress tolerance.

plant biology↗

bioRxiv2023

Intranasal CRMP2-Ubc9 Inhibitor Regulates NaV1.7 to Alleviate Trigeminal Neuropathic Pain

Dysregulation of voltage-gated sodium NaV1.7 channels in sensory neurons contributes to chronic pain conditions, including trigeminal neuropathic pain. We previously reported that chronic pain results in part from increased SUMOylation of collapsin response mediator protein 2 (CRMP2), leading to an increased CRMP2/NaV1.7 interaction and increased functional activity of NaV1.7. Targeting this feed-forward regulation, we developed compound 194, which inhibits CRMP2 SUMOylation mediated by the SUMO-conjugating enzyme Ubc9. We further demonstrated that 194 effectively reduces the functional activity of NaV1.7 channels in dorsal root ganglia neurons and alleviated inflammatory and neuropathic pain. Here, we employed a comprehensive array of investigative approaches, encompassing biochemical, pharmacological, genetic, electrophysiological, and behavioral analyses, to assess the functional implications of NaV1.7 regulation by CRMP2 in trigeminal ganglia (TG) neurons. We confirmed the expression of Scn9a, Dpysl2, and UBE2I within TG neurons. Furthermore, we found an interaction between CRMP2 and NaV1.7, with CRMP2 being SUMOylated in these sensory ganglia. Disrupting CRMP2 SUMOylation with compound 194 uncoupled the CRMP2/NaV1.7 interaction, impeded NaV1.7 diffusion on the plasma membrane, and subsequently diminished NaV1.7 activity. Compound 194 also led to a reduction in TG neuron excitability. Finally, when intranasally administered to rats with chronic constriction injury of the infraorbital nerve (CCI-ION), 194 significantly decreased nociceptive behaviors. Collectively, our findings underscore the critical role of CRMP2 in regulating NaV1.7 within TG neurons, emphasizing the importance of this indirect modulation in trigeminal neuropathic pain.

neuroscience↗

bioRxiv2022

Effects of cardiac function alterations on the risk of postoperative thrombotic complications in patients receiving endovascular aortic repair

Chronic heart disease (CHD) is a common comorbidity of patients receiving endovascular aneurysm repair (EVAR) for abdominal aortic aneurysms (AAA). The ventricular systolic function determines the hemodynamic environments in aorta, and thus regulating the formation of postoperative thrombus. However, the explicit relationship between ventricular systolic function and EVAR complication of thrombotic events is unknown. Here, we proposed a three-dimensional numerical model coupled with the lumped-elements heart model, which is capable of simulating thrombus formation in diverse systolic functions. The computational results demonstrate that thrombus tended to form on the interior side of the aorta arch and iliac branches, which is consistent with the four patients post-operative imaging follow-up. In addition, we found that the thrombus formation has negative correlations with the maximum ventricular contractile force (r=-0.2814{+/-}0.1012) and positive correlations with the minimum ventricular contractile force (r=0.238{+/-}0.074), whereas the effect of heart rate (r=-0.0148{+/-}0.1211) on thrombus formation is not significant. In conclusion, changes in ventricular systolic function may alter the risk of thrombotic events after EVAR repair, which could provide insight into the selection of adjuvant therapy strategies for AAA patients with CHD.

bioengineering↗

bioRxiv2022

A permissive role for dopamine in the production of vigorous movements

Dopamine is essential for the production of vigorous movements, but how dopamine modifies the gain of motor commands remains unclear. Here, we developed a dexterous motor task in which head-restrained mice self-initiate fast and large-amplitude lever pushes with their left forelimb to earn rewards. We show that this task is goal-directed and depends on cortico-striatal circuits in the hemisphere contralateral to the limb used to push the lever. We find that unilateral loss of midbrain dopamine neurons reduces the speed and amplitude of lever pushes, and that levodopa treatment rapidly restores motor vigor, consistent with parkinsonian bradykinesia. Photometry recordings of striatal dopamine levels indicate that the therapeutic efficacy of levodopa does not require phasic dopamine release. In dopamine-intact mice, optogenetic stimulation of midbrain dopamine neurons calibrated to mimic transients evoked by rewards is also insufficient to increase the speed and amplitude of forelimb movements. Together, our data show that phasic dopamine transients are unlikely to specify the vigor of forelimb movements online as they are being executed, and suggest instead that dopamine plays a permissive role in the selection and production of vigorous movements. Our findings have important implications for our understanding of how the basal ganglia contribute to motor control under physiological conditions and in Parkinsons disease.

neuroscience↗

bioRxiv2022

A small-molecule lycorine derivative reveals Na+/K+-ATPase α3 as an anti-obesity target

Obesity remains a severe global public health challenge, with contemporary therapeutic approaches primarily focusing on appetite suppression. Here, we discovered HLY72, a lycorine-derived small molecule that potently counteracts obesity in mice at doses without affecting food intake, by promoting sympathetic activation-mediated lipolysis and thermogenesis in adipose tissues. Mass spectrometry identified Na+/K+-ATPase (NKA) 3, the brain-specific isoform, as HLY72s target. Only blood-brain barrier-permeable NKA inhibitors reproduce HLY72s anti-obesity effects, and resistance to HLY72 treatment occurs specifically in NKA 3 (not 1) knockin mice harboring a HLY72-binding mutation. Similar to the chemical inhibition by HLY72, genetic inhibition of NKA 3 also effectively protects mice from diet-induced obesity. These findings point NKA 3 as a potent anti-obesity drug target and highlight HLY72s potential in treating and preventing obesity independent of appetite control.

physiology↗

bioRxiv2022

The genome of a vestimentiferan tubeworm (Ridgeia piscesae) provides insights into its adaptation to a deep-sea environment

Vestimentifera (Polychaeta, Siboglinidae) is a taxon of deep-sea worm-like animals living in the deep-sea hydrothermal vent and cold seep areas. The morphology and lifespan of Ridgeia piscesae, which is the only vestimentiferan tubeworm species found in the hydrothermal vents on the Juan de Fuca Ridge, vary greatly according to the endemic environments. Recent analyses have revealed the genomic basis of adaptation in three vent- and seep-dwelling vestimentiferan tubeworms. However, the evolutionary history and mechanism of adaptation in R. piscesae, a unique species in the family Siboglinidae, is remained to be investigated. Here we report a high-quality genome of R. piscesae collected at Cathedral vent of the Juan de Fuca Ridge. Comparative genomic analysis revealed that that the high growth rates of vent-dwelling tubeworms might derive from small genome size. The small genome sizes of these tubeworms are attributed to the repeat content but not the number of genes and intron sizes. Additionally, four genes involved in cell proliferation were subject to positive selection in the genome of R. piscesae, suggesting that, besides apoptosis, cell proliferation is important for regulating growth rate in this species.

genomics↗

bioRxiv2022

Building a Tissue-unbiased Brain Template of Fibre Orientation Distribution and Tractography with Multimodal Registration

A brain template provides a standard space for statistical analysis of brain structure and function. For decades, the T1- and T2-weighted brain templates have been widely used for brain grey matter anatomical and functional analysis. However, T1- and T2-weighted templates provide very limited information about the axonal organization within the white matter. Recent advances in Diffusion MRI have enabled the detailed modelling of the axonal fibre orientation distribution (FOD) in white matter. Therefore, building a FOD template is essential for more robust white matter anatomy related analysis; however, it is important that this template aligns well with the cortical and subcortical structures. From such a FOD template, a tractography template can be also generated by fibre tracking algorithms, which can be used for subsequent applications, such as to perform the joint structural and functional analysis while ensuring rigorous fibre-to-fibre correspondence. In this paper, we explore the potential of generating the FOD template based on multimodal registration, in order to constrain the tempalte unbiased to both white and grey matter. We combine the information from T1-weighted, T2-weighted and Diffusion MRI to generate a coherent transformation for FOD registration and template generation. Our FOD template preserves the structural details at the white-grey matter boundary. To illustrate the benefit of this new approach, the resulting tractography template was used for joint structural-functional connectivity analysis.

neuroscience↗

bioRxiv2021

Identification of the Novel Pyroptosis-Related Gene Signature in Patients with Esophageal Adenocarcinoma

Esophageal adenocarcinoma (EAC) is a highly malignant type of digestive tract cancers with a poor prognosis despite therapeutic advances. Pyroptosis is an inflammatory form of programmed cell death, whereas the role of pyroptosis in EAC remains largely unknown. Herein, we identified a pyroptosis-related five-gene signature that was significantly correlated with the survival of EAC patients in The Cancer Genome Atlas (TCGA) cohort and an independent validation dataset. In addition, a nomogram based on the five-gene signature was constructed with novel prognostic values. Moreover, the genes in the pyroptosis-related signature, CASP1, GSDMB, IL1B, PYCARD, and ZBP1, might be involved in immune response and regulation of the tumor microenvironment. Our findings indicate that the five-gene signature provides insights into the involvement of pyroptosis in EAC progression, and is promising in the risk assessment as well as prognosis for EAC patients in clinical practice.

bioinformatics↗

bioRxiv2021

FOD-Net: A Deep Learning Method for Fiber Orientation Distribution Angular Super Resolution

Mapping the human connectome using fiber-tracking permits the study of brain connectivity and yields new insights into neuroscience. However, reliable connectome reconstruction using diffusion magnetic resonance imaging (dMRI) data acquired by widely available clinical protocols remains challenging, thus limiting the connectome / tractography clinical applications. Here we develop fiber orientation distribution (FOD) network (FOD-Net), a deep-learning-based framework for FOD angular super-resolution. Our method enhances the angular resolution of FOD images computed from common clinical-quality dMRI data, to obtain FODs with quality comparable to those produced from advanced research scanners. Super-resolved FOD images enable superior tractography and structural connectome reconstruction from clinical protocols. The method was trained and tested with high-quality data from the Human Connectome Project (HCP) and further validated with a local clinical 3.0T scanner. Using this method, we improve the angular resolution of FOD images acquired with typical single-shell low-angular-resolution dMRI data (e.g., 32 directions, b = 1000 s/mm2) to approximate the quality of FODs derived from time-consuming, multi-shell high-angular-resolution dMRI research protocols. We also demonstrate tractography improvement, removing spurious connections and bridging missing connections. We further demonstrate that connectomes reconstructed by super-resolved FODs achieve comparable results to those obtained with more advanced dMRI acquisition protocols, on both HCP and clinical 3.0T data. Advances in deep-learning approaches used in FOD-Net facilitate the generation of high quality tractography / connectome analysis from existing clinical MRI environments. Our code is freely available at https://github.com/ruizengalways/FOD-Net.

bioengineering↗

bioRxiv2020

Momilactone B inhibits Arabidopsis growth and development via disruption of ABA and auxin signaling

In competition for limited resources, many plants release allelochemicals to inhibit the growth of neighboring plants. Momilactone B (MB) is a major allelochemical produced by rice (Oryza sativa), however its mode of action is currently unknown. We used Arabidopsis (Arabidopsis thaliana) as a model system to evaluate potential mechanisms underlying the inhibitory effects of MB on seed germination, seedling establishment and root growth through the use of confocal microscopy and the examination of transcriptional responses in MB-treated seedlings. In response to MB treatment, transcript levels for genes encoding several key ABA biosynthetic enzymes and signaling components, including the transcription factor ABA-INSENSITIVE 4 (ABI4), were dramatically increased. Additionally, ABA insensitive 4 (abi4) mutant seedlings exhibited reduced susceptibility to exogenously-provided MB. Although the transcript levels of DELLA genes, which negatively regulate GA signaling, were significantly increased upon MB exposure, exogenous GA application did not reverse the inhibitory effects of MB on Arabidopsis germination and seedling development. Moreover, a reduction in seedling root meristematic activity, associated with reduced expression of auxin biosynthetic genes and efflux transporters, and apparent lowered auxin content, was observed in MB-treated root tips. Exogenous auxin applications partially rescued the inhibitory effects of MB observed in root growth. Our results indicate that MB suppresses Arabidopsis seed germination and root growth primarily via disruption of ABA and auxin signaling. These findings underscore the crucial roles played by phytohormones in mediating responses to allelochemical exposure. One-sentence summaryMomilactone B, the key allelochemical of rice, inhibits Arabidopsis growth and development via disruption of ABA and auxin signaling, suggesting the crucial roles of phytohormones in plant allelopathy

plant biology↗

bioRxiv2020

Proteomics of protein trafficking by in vivo tissue-specific labeling

Secreted interorgan communication factors encode key regulators of homeostasis. However, long-standing questions surround their origins/destinations, mechanisms of interactions, and the number of proteins involved. Progress has been hindered by the lack of methodologies for these factors large-scale identification and characterization, as conventional approaches cannot identify low-abundance factors and the origins and destinations of secreted proteins. We established an in vivo platform to investigate secreted protein trafficking between organs proteome-wide, whereby engineered promiscuous biotin ligase BirA*G3 (a relative of TurboID) biotinylates all proteins in a subcellular compartment of one tissue, and biotinylated proteins are affinity-enriched and identified from distal organs using quantitative mass spectrometry. Using this platform, we identified 51 putative muscle-secreted proteins from heads and 269 fat body-secreted proteins from legs/muscles, of which 60-70% have human orthologs. We demonstrate, in particular, that conserved fat body-derived novel interorgan communication factors CG31326, CG2145, and CG4332 promote muscle activity. Our results indicate that the communication network of secreted proteins is vast, and we identified systemic functions for a number of these factors. This approach is widely applicable to studies in interorgan, local and intracellular protein trafficking networks, non-conventional secretion, and to mammalian systems, under healthy or diseased states. One Sentence SummaryWe developed an in vivo platform to investigate protein trafficking between organs proteome-wide, provide a resource for interorgan communication factors, and determined conserved adipokines that affect muscles.

physiology↗