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Cited by 6Cellular transport and secretionBioinformatics and Genomic NetworksEndoplasmic Reticulum Stress and Disease

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A reconstruction of the mammalian secretory pathway identifies mechanisms regulating antibody production

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Masson, Helen, Tat, Jasmine, Di Giusto, Pablo, Antonakoudis, Athanasios, Shamie, Isaac, Baghdassarian, Hratch, Samoudi, Mojtaba, Robinson, Caressa M., Kuo, Chih-Chung, Koga, Natalia, Singh, Sonia, Gezalyan, Angel, Li, Zerong, Movsessian, Alexia, Richelle, Anne, Lewis, Nathan E.·2025·Cell Systems
DOI 10.1016/j.cels.2025.101453PMC PMC12704830

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Abstract

The secretory pathway processes >30% of mammalian proteins, orchestrating their synthesis, modification, trafficking, and quality control across multiple organelles via coordinated interactions, making its regulation difficult to decipher. To advance such research, we present secRecon, a reconstruction of the mammalian secretory pathway, comprising 1,127 manually curated genes organized within 77 secretory process terms, annotated with functional roles, subcellular localization, protein interactions, and complexes. Applying secRecon to omics data revealed distinct secretory topologies in antibody-producing plasma cells versus Chinese hamster ovary (CHO) cells, with CHO-specific deficiencies in proteostasis, translocation, and N-glycosylation genes, highlighting targets to enhance secretion. Analysis of single-cell SEC-seq data uncovered diversity in IgG-secreting plasma cells that is shaped by the unfolded protein response, endoplasmic reticulum (ER)-associated degradation, and vesicle trafficking and identified distinct secretory machinery genes as markers of plasma cell differentiation. These results show that secRecon enables the discovery of mechanisms controlling protein secretion and supports applications in both biomedical research and biotechnology. A record of this paper's transparent peer review process is included in the supplemental information.

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Metadata

Authors
Masson, H., Tat, J., Di Giusto, P., Antonakoudis, A., Shamie, I., Baghdassarian, H., Samoudi, M., Robinson, C. M., Kuo, C.-C., Koga, N., Singh, S., Gezalyan, A., Li, Z., Movsessian, A., Richelle, A., & Lewis, N. E.
Affiliations
  • University of California San Diego (US)
  • Sartorius (United Kingdom) (GB)
  • University of Georgia (US)
Corresponding author
Lewis, Nathan E.
ORCID
Venue
Cell Systems
Publisher
Elsevier BV
Published
2025-12
Volume
16
Issue
12
Pages
101453
ISSN
2405-4712 (ISSN-L)
DOI
10.1016/j.cels.2025.101453
PMC
PMC12704830
OpenAlex
W4417198380
Cited by
6
References
7
Citations by year
2026: 4 · 2025: 2
FWCI
3.00
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Systems (publishedVersion)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion)
Funders
  • National Science Foundation (CBET-2030039)
  • Novo Nordisk Foundation (NNF20SA0066621)
  • National Institutes of Health
  • National Institute of General Medical Sciences (R35 GM119850)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
Keywords
secretory pathway, protein secretion, antibody production, plasma cells, gene ontology annotation, N-glycosylation, proteostasis, unfolded protein response, ER-associated degradation, vesicle trafficking, plasma cell differentiation, CHO cells, protein quality control
MeSH terms
Animals, Antibody Formation, Cricetulus, Endoplasmic Reticulum, Humans, Mammals, Plasma Cells, CHO Cells, Protein Transport, Secretory Pathway, Unfolded Protein Response

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