Using multifocal plane microscopy to reveal novel trafficking processes in the recycling pathway
Open accessAbstract
Summary: A major outstanding issue in cell biology is the lack of understanding of the contribution of tubulovesicular transport carriers (TCs) to intracellular trafficking pathways within 3D cellular environments. This is primarily due to the challenges associated with the use of microscopy techniques to track these highly motile, small compartments. In the present study we have used multifocal plane microscopy with localized photoactivation to overcome these limitations. Using this approach, we have characterized individual components constituting the recycling pathway of the receptor FcRn. Specifically, several different pathways followed by TCs that intersect with larger, relatively static sorting endosomes have been defined. These pathways include a novel ‘looping’ process in which TCs leave and return to the same sorting endosome. Significantly, TCs with different itineraries can be identified by associations with distinct complements of Rab GTPases, APPL1 and SNX4. These studies provide a framework for further analyses of the recycling pathway.
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Monomeric IgG bound to FcRn is directed into sorting tubules and back to the cell surface.
“which then directs monomeric IgG bound to FcRn into sorting tubules and, ultimately, back to the cell surface.”
From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [5]
The Introduction (page unavailable) says the FcRn–IgG complex is recycled to the cell surface, and the Results (page unavailable) describe FcRn leaving sorting endosomes in tubulovesicular carriers. The copy does not establish that the IgG in those carriers is specifically monomeric or directly track bound IgG through the post-sorting tubules. (LLM, conf=0.84)
Experimental — accuracy not yet measuredThe site of IgG salvage is the recycling (or sorting) endosome.
“Studies employing cellular imaging of fluorescently labeled proteins have shown that the site of IgG salvage is the recycling (or sorting) endosome [5–7]”
From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [5]
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Cell surface dynamics and cellular distribution of endogenous FcRn
D’Hooghe, L., Chalmers, A. D., Heywood, S., & Whitley, P. (2017) · PLOS ONE · doi:10.1371/journal.pone.0182695 · Cited by 42 · see citing works
Sirina, J., D'Hooghe, L. E., Singhvi-Hanns, L. A., Cole, S. L., Shock, A., Holliday, N. D., & Stoddart, L. A. (2026) · Cellular Immunology · doi:10.1016/j.cellimm.2026.105128
- Authors
- Gan, Z., Ram, S., Ober, R. J., & Ward, E. S.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- The University of Texas at Dallas (US)
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2013-03-01
- Volume
- 126
- Issue
- 5
- Pages
- 1176-1188
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- PMC
- PMC3635461
- OpenAlex
- W2023934984
- Cited by
- 38
- References
- 3
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 4 · 2021: 5 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 2 · 2016: 2 · 2015: 5 · 2014: 4
- FWCI
- 2.13
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Cell Science (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Funders
- National Institute of General Medical Sciences (R0I GM085575, R01GM085575)
- National Institute of Allergy and Infectious Diseases (R01AI039167, R0I AI039167)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR056478, R0I AR056478)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- recycling pathway, neonatal Fc receptor, sorting endosomes, intracellular trafficking, Rab GTPases, APPL1, SNX4, photoactivated localization microscopy
- MeSH terms
- Cell Line, Humans, Microscopy, Endosomes, rab GTP-Binding Proteins, Adaptor Proteins, Signal Transducing, Sorting Nexins
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