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Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level

Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level
Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level

IgG transport within and across cells is essential for effective humoral immunity. Through a combination of biochemical and in vivo analyses, the MHC class I-related neonatal Fc receptor (FcRn) is known to play a central role in delivering IgGs within and across cells. However, little is known about the molecular and cellular mechanisms that are involved in the exocytosis of IgG from cells that express FcRn. Here, we use single-molecule fluorescence microscopy to analyze exocytic processes in FcRn-GFP-transfected human endothelial cells. We show that exocytosis can occur by means of multiple modes that range from complete fusion of the exocytic vesicle with the plasma membrane to a slower-release mode ("prolonged release") that only involves partial mixing of membrane contents. Even for prolonged release, diffusion of FcRn into the plasma membrane can occur, indicating that FcRn is directly involved in IgG exocytosis. The slower-release mode is characterized by periodic, stepwise release of IgG, rather than the rapid burst that is observed for complete-fusion events. Analyses of single-molecule tracks suggest that IgG may be bound to FcRn for several seconds after exocytosis. Unexpectedly, after diffusion out of the exocytic site, IgG and FcRn molecules can also migrate back into the epicenter of the release site. Such retrograde movement may represent a mechanism for FcRn retrieval. Our studies provide insight into the events that lead to IgG exocytosis.

0027-8424
11076-11081
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Martinez, Cruz
cbab0de7-7dc0-4444-959e-37e41588563f
Lai, Xuming
b0521079-5b4e-4939-ab03-0d0bb5a0e022
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc
Ober, Raimund J.
31f4d47f-fb49-44f5-8ff6-87fc4aff3d36
Martinez, Cruz
cbab0de7-7dc0-4444-959e-37e41588563f
Lai, Xuming
b0521079-5b4e-4939-ab03-0d0bb5a0e022
Zhou, Jinchun
373ef03a-4fb7-4022-98c2-7332251c5c30
Ward, E. Sally
b31c0877-8abe-485f-b800-244a9d3cd6cc

Ober, Raimund J., Martinez, Cruz, Lai, Xuming, Zhou, Jinchun and Ward, E. Sally (2004) Exocytosis of IgG as mediated by the receptor, FcRn: An analysis at the single-molecule level. Proceedings of the National Academy of Sciences of the United States of America, 101 (30), 11076-11081. (doi:10.1073/pnas.0402970101).

Record type: Article

Abstract

IgG transport within and across cells is essential for effective humoral immunity. Through a combination of biochemical and in vivo analyses, the MHC class I-related neonatal Fc receptor (FcRn) is known to play a central role in delivering IgGs within and across cells. However, little is known about the molecular and cellular mechanisms that are involved in the exocytosis of IgG from cells that express FcRn. Here, we use single-molecule fluorescence microscopy to analyze exocytic processes in FcRn-GFP-transfected human endothelial cells. We show that exocytosis can occur by means of multiple modes that range from complete fusion of the exocytic vesicle with the plasma membrane to a slower-release mode ("prolonged release") that only involves partial mixing of membrane contents. Even for prolonged release, diffusion of FcRn into the plasma membrane can occur, indicating that FcRn is directly involved in IgG exocytosis. The slower-release mode is characterized by periodic, stepwise release of IgG, rather than the rapid burst that is observed for complete-fusion events. Analyses of single-molecule tracks suggest that IgG may be bound to FcRn for several seconds after exocytosis. Unexpectedly, after diffusion out of the exocytic site, IgG and FcRn molecules can also migrate back into the epicenter of the release site. Such retrograde movement may represent a mechanism for FcRn retrieval. Our studies provide insight into the events that lead to IgG exocytosis.

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More information

e-pub ahead of print date: 16 July 2004
Published date: 27 July 2004

Identifiers

Local EPrints ID: 424080
URI: http://eprints.soton.ac.uk/id/eprint/424080
ISSN: 0027-8424
PURE UUID: 967b7c34-aab2-45ba-ae0e-e963c00d4db8
ORCID for Raimund J. Ober: ORCID iD orcid.org/0000-0002-1290-7430
ORCID for E. Sally Ward: ORCID iD orcid.org/0000-0003-3232-7238

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Date deposited: 04 Oct 2018 16:30
Last modified: 16 Mar 2024 04:37

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Contributors

Author: Raimund J. Ober ORCID iD
Author: Cruz Martinez
Author: Xuming Lai
Author: Jinchun Zhou
Author: E. Sally Ward ORCID iD

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