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Cited by 76Cellular transport and secretionAutophagy in Disease and TherapyCalcium signaling and nucleotide metabolism

Analyses of the recycling receptor, FcRn, in live cells reveal novel pathways for lysosomal delivery

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Gan, Zhuo, Ram, Sripad, Vaccaro, Carlos, Ober, Raimund J., Ward, E. Sally·2009·Traffic
DOI 10.1111/j.1600-0854.2009.00887.xPMC PMC2813311
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Abstract

Lysosomes play a central role in the degradation of proteins and other macromolecules. The mechanisms by which receptors are transferred to lysosomes for constitutive degradation are poorly understood. We have analyzed the processes that lead to the lysosomal delivery of the Fc receptor, FcRn. These studies provide support for a novel pathway for receptor delivery. Specifically, unlike other receptors that enter intraluminal vesicles in late endosomes, FcRn is transferred from the limiting membrane of such endosomes to lysosomes, and is rapidly internalized into the lysosomal lumen. By contrast, LAMP-1 persists on the limiting membrane. Receptor transfer is mediated by tubular extensions from late endosomes to lysosomes, or by interactions of the two participating organelles in kiss-and-linger-like processes, whereas full fusion is rarely observed. The persistence of FcRn on the late endosomal limiting membrane, together with selective transfer to lysosomes, allows this receptor to undergo recycling or degradation. Consequently, late endosomes have functional plasticity, consistent with the presence of the Rab5 GTPase in discrete domains on these compartments.

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  • Rab5 and Rab7 colocalize with FcRn inhibitor uptake in endothelial cells.

    “Our findings of Rab5 and Rab7 colocalization on FcRn inhibitor uptake are consistent with those of Gan and co-workers [37] using over-expressed, transfected FcRn in endothelial cells, identified with fluorescent labeled MST-HN IgG Fc.”

    From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [37]

    The Results section, “Persistence of Rab5 on fusion competent, late endosomes” (page unavailable), reports Rab5 on FcRn-positive endosomes and Rab7 on late endosomes in transfected HMEC-1 endothelial cells. “Temporal aspects of lysosomal delivery” describes fluorescent MST-HN IgG as a tracer for FcRn, not an FcRn inhibitor; the paper therefore supports the trafficking comparison but not the claim about inhibitor uptake. (LLM, conf=0.86)

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  • Investigating the return of recycled FcRn to the cell surface is problematic in endothelial cells, largely due to low cell surface expression and slow kinetics of intracellular FcRn return, which has necessitated (over)transfection of FcRn to study such pathways in endothelial cells.

    “Investigating the return of recycled FcRn to the cell surface has proved to be problematic in endothelial cells, largely due to the low cell surface expression and the slow kinetics for the return of intracellular FcRn, which, for practical reasons, has necessitated (over)transfection of FcRn to study such pathways in endothelial cells [6,8,37,39].”

    From The uptake, intracellular trafficking and recycling of FcRn-blocking therapeutics in human endothelial cells in vitro (2026) · cites this paper as [37]

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Authors
Gan, Z., Ram, S., Vaccaro, C., Ober, R. J., & Ward, E. S.
Affiliations
  • The University of Texas Southwestern Medical Center (US)
  • The University of Texas at Dallas (US)
Corresponding author
  • Ober, Raimund J.
  • Ward, E. Sally
ORCID
Venue
Traffic
Publisher
Wiley
Published
2009-04-08
Volume
10
Issue
5
Pages
600-614
ISSN
  • 1398-9219 (ISSN-L)
  • 1600-0854
DOI
10.1111/j.1600-0854.2009.00887.x
PMC
PMC2813311
OpenAlex
W2042041059
Cited by
76
References
2
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 6 · 2021: 5 · 2020: 2 · 2019: 3 · 2018: 6 · 2017: 5 · 2016: 1 · 2015: 10 · 2014: 7 · 2013: 5 · 2012: 6
FWCI
2.67
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Traffic (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • ePrints Soton (University of Southampton) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (R01GM071048)
  • National Institute of Allergy and Infectious Diseases (R01AI039167)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
Keywords
neonatal Fc receptor, lysosomal delivery, late endosomes, lysosomes, limiting membrane, LAMP1, endosomal membrane fusion, Rab5 GTPase, receptor recycling, protein degradation, intraluminal vesicles
MeSH terms
Animals, Humans, Intracellular Membranes, Lysosomes, Receptors, Fc, Endosomes, Signal Transduction, Mice

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