The recycling and transcytotic pathways for IgG transport by FcRn are distinct and display an inherent polarity
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The Fc receptor FcRn traffics immunoglobulin G (IgG) in both directions across polarized epithelial cells that line mucosal surfaces, contributing to host defense. We show that FcRn traffics IgG from either apical or basolateral membranes into the recycling endosome (RE), after which the actin motor myosin Vb and the GTPase Rab25 regulate a sorting step that specifies transcytosis without affecting recycling. Another regulatory component of the RE, Rab11a, is dispensable for transcytosis, but regulates recycling to the basolateral membrane only. None of these proteins affect FcRn trafficking away from lysosomes. Thus, FcRn transcytotic and recycling sorting steps are distinct. These results are consistent with a single structurally and functionally heterogeneous RE compartment that traffics FcRn to both cell surfaces while discriminating between recycling and transcytosis pathways polarized in their direction of transport.
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Different proteins are involved in regulating FcRn-mediated IgG transcytosis (actin motor myosin Vb and Rab25) and recycling (Rab11a).
“different proteins are involved in regulating FcRn-mediated IgG transcytosis (actin motor myosin Vb and Rab25) and recycling (Rab11a), respectively (75).”
From Factors Affecting the FcRn-Mediated Transplacental Transfer of Antibodies and Implications for Vaccination in Pregnancy (2017) · cites this paper as [75]
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Claypool, S. M., Dickinson, B. L., Wagner, J. S., Johansen, F.-E., Venu, N., Borawski, J. A., Lencer, W. I., & Blumberg, R. S. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-11-0832 · Cited by 139 · see citing works
Self-citationRaghavan, M., Gastinel, L. N., & Bjorkman, P. J. (1993) · Biochemistry · doi:10.1021/bi00084a037 · Cited by 108 · see citing works
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Wilcox, C. R., Holder, B., & Jones, C. E. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01294 · Cited by 200 · see citing works
“One possible explanation relates to recent findings suggesting that different proteins are involved in regulating FcRnmediated IgG transcytosis (actin motor myosin Vb and Rab25) and recycling (Rab11a), respectively (75).”
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- Authors
- Tzaban, S., Massol, R. H., Yen, E., Hamman, W., Frank, S. R., Lapierre, L. A., Hansen, S. H., Goldenring, J. R., Blumberg, R. S., & Lencer, W. I.
- Affiliations
- Brigham and Women's Hospital (US)
- Vanderbilt University (US)
- Corresponding author
- Lencer, Wayne I.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2009-05-18
- Volume
- 185
- Issue
- 4
- Pages
- 673-684
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2711563
- OpenAlex
- W2137960793
- Cited by
- 169
- References
- 2
- Citations by year
- 2026: 4 · 2025: 9 · 2024: 8 · 2023: 4 · 2022: 9 · 2021: 10 · 2020: 11 · 2019: 8 · 2018: 8 · 2017: 16 · 2016: 9 · 2015: 19 · 2014: 10 · 2013: 13 · 2012: 12
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (DK53056)
- Harvard Digestive Diseases Center, Harvard University (P30DK034854, DK034854)
- National Cancer Institute (R01CA092354, CA092354)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-070856, R56DK070856, R01DK084424, R01DK070856, R01DK053056, R01 DK53056, R01DK-48370, P30DK034854, R01DK048370, P30DK040561)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Keywords
- neonatal Fc receptor, IgG transport, transcytosis, recycling endosomes, epithelial polarity, MYO5B, Rab25, Rab11a, mucosal immunity, lysosomal escape
- MeSH terms
- rab11 GTP-Binding Proteins, Animals, Cell Compartmentation, Cell Line, Cell Membrane, Dogs, Humans, Immunoglobulin G, Receptors, Fc, Endosomes, Cell Polarity, Myosin Heavy Chains, rab GTP-Binding Proteins, Protein Transport, Myosin Type V
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