Dual‐Organelle Secretome Conjugation and Organ‐Uptake Tracking (DuO‐SCOUT) Enables Deep and Sensitive Mapping of the Secreted Proteins
- 1Department of Biomedical Sciences College of Biomedicine City University of Hong Kong Hong Kong Hong Kong SAR China
- 2Biotech and Health Centre Shenzhen Research Institute of City University of Hong Kong Shenzhen Guangdong China
- 3Department of Neuroscience College of Biomedicine City University of Hong Kong Hong Kong Hong Kong SAR China
Abstract
Inter‐organ communication is governed by a complex “secretome,” yet mapping the journey of these factors from their origin to precise cellular destinations remains a fundamental challenge. Proximity labeling emerges as a powerful tool to dissect the secretome, yet conventional workflows typically rely on single‐compartment biotinylation at the endoplasmic reticulum (ER), failing to capture proteins that utilize unconventional secretion. Here, we present DuO‐SCOUT (Dual‐Organelle Secretome Conjugation and Organ‐Uptake Tracking), a high‐performance platform that simultaneously targets BioID2 to the ER and the trans‐Golgi network (TGN). This integrated strategy captures the full secretory maturation relay, increasing protein identification by over 120% compared to traditional ER‐anchored methods. We translated this in vivo using an Adipoq‐Cre mouse model to map the adipose secretome. To bridge the gap between systemic transport and tissue‐specific uptake, DuO‐SCOUT integrates BSPA (Biotin‐Specific Proximity Amplification), a visualization toolkit detecting biotinylated proteins with sub‐nanomolar sensitivity. In obese mice, we identified the piriform cortex (PIR) as a previously unrecognized extra‐hypothalamic sink for adipose‐derived leptin. This is associated with a localized neuroinflammatory signature, including significant induction of Il6. DuO‐SCOUT establishes a broadly applicable framework for dissecting the complex molecular logic of systemic organ‐organ communication.
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BibTeX
@article{yang2026dualorganelle,
title = {{Dual‐Organelle Secretome Conjugation and Organ‐Uptake Tracking (DuO‐SCOUT) Enables Deep and Sensitive Mapping of the Secreted Proteins}},
author = {Fenglian Yang and Rui Qian and Jiaxing Song and Xingqi Meng and Jin Young Kim and Kwok On Lai and Li Wang and Liang Zhang},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77190},
url = {https://doi.org/10.1002/advs.77190},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Dual‐Organelle Secretome Conjugation and Organ‐Uptake Tracking (DuO‐SCOUT) Enables Deep and Sensitive Mapping of the Secreted Proteins
AU - Fenglian Yang
AU - Rui Qian
AU - Jiaxing Song
AU - Xingqi Meng
AU - Jin Young Kim
AU - Kwok On Lai
AU - Li Wang
AU - Liang Zhang
PY - 2026
DA - 2026/08/14
JO - Advanced Science
DO - 10.1002/advs.77190
UR - https://doi.org/10.1002/advs.77190
AB - Inter‐organ communication is governed by a complex “secretome,” yet mapping the journey of these factors from their origin to precise cellular destinations remains a fundamental challenge. Proximity labeling emerges as a powerful tool to dissect the secretome, yet conventional workflows typically rely on single‐compartment biotinylation at the endoplasmic reticulum (ER), failing to capture proteins that utilize unconventional secretion. Here, we present DuO‐SCOUT (Dual‐Organelle Secretome Conjugation and Organ‐Uptake Tracking), a high‐performance platform that simultaneously targets BioID2 to the ER and the trans‐Golgi network (TGN). This integrated strategy captures the full secretory maturation relay, increasing protein identification by over 120% compared to traditional ER‐anchored methods. We translated this in vivo using an Adipoq‐Cre mouse model to map the adipose secretome. To bridge the gap between systemic transport and tissue‐specific uptake, DuO‐SCOUT integrates BSPA (Biotin‐Specific Proximity Amplification), a visualization toolkit detecting biotinylated proteins with sub‐nanomolar sensitivity. In obese mice, we identified the piriform cortex (PIR) as a previously unrecognized extra‐hypothalamic sink for adipose‐derived leptin. This is associated with a localized neuroinflammatory signature, including significant induction of Il6. DuO‐SCOUT establishes a broadly applicable framework for dissecting the complex molecular logic of systemic organ‐organ communication.
SN - 2198-3844
ER -