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Electron tomography of late stages of FcRn-mediated antibody transcytosis in neonatal rat small intestine

Ladinsky, Mark S. and Huey-Tubman, Kathryn E. and Bjorkman, Pamela J. (2012) Electron tomography of late stages of FcRn-mediated antibody transcytosis in neonatal rat small intestine. Molecular Biology of the Cell, 23 (13). pp. 2537-2545. ISSN 1059-1524. PMCID PMC3386217. https://resolver.caltech.edu/CaltechAUTHORS:20120807-121958516

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Abstract

The neonatal Fc receptor (FcRn) transports maternal immunoglobulin (IgG) across epithelia to confer passive immunity to mammalian young. In newborn rodents, FcRn transcytoses IgG from ingested milk across the intestinal epithelium for release into the bloodstream. We used electron tomography to examine FcRn transport of Nanogold-labeled Fc (Au-Fc) in neonatal rat jejunum, focusing on later aspects of transport by chasing Au-Fc before fixation. We observed pools of Au-Fc in dilated regions of the lateral intercellular space (LIS), likely representing exit sites where Au-Fc accumulates en route to the blood. Before weaning, the jejunum functions primarily in IgG transport and exhibits unusual properties: clathrin-rich regions near/at the basolateral LIS and multivesicular bodies (MVBs) expressing early endosomal markers. To address whether these features are related to IgG transport, we examined LIS and endocytic/transcytotic structures from neonatal and weaned animals. Weaned samples showed less LIS-associated clathrin. MVBs labeled with late endosomal/lysosomal markers were smaller than their neonatal counterparts but contained 10 times more internal compartments. These results are consistent with hypotheses that clathrin-rich basolateral regions in neonatal jejunum are involved in IgG exocytosis and that MVBs function in IgG transport while FcRn is expressed but switch to degradative functions after weaning, when the jejunum does not express FcRn or transport IgG.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1091/mbc.E12-02-0093DOIArticle
http://www.molbiolcell.org/content/23/13/2537PublisherArticle
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386217/PubMed CentralArticle
ORCID:
AuthorORCID
Ladinsky, Mark S.0000-0002-1036-3513
Huey-Tubman, Kathryn E.0000-0002-4683-8138
Bjorkman, Pamela J.0000-0002-2277-3990
Additional Information:© 2012 Ladinsky et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. Received: Feb 7, 2012; Revised: Apr 4, 2012; Accepted: May 1, 2012. Published online before print May 9, 2012. This article was published online ahead of print in MBoC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E12-02-0093) on May 9, 2012. We thank Grant Jensen and his laboratory for use of the transmission electron microscope and Nathan F. Dalleska and the Caltech Environmental Analysis Center (Pasadena, CA) for assistance with ICP-MS. This work was supported by the National Institutes of Health (2 R37 AI041239-06A1 to P.J.B.) and gifts from the Gordon and Betty Moore Foundation and the Agouron Institute to support electron microscopy at Caltech.
Funders:
Funding AgencyGrant Number
NIH2 R37 AI041239-06A1
Gordon and Betty Moore FoundationUNSPECIFIED
Agouron InstituteUNSPECIFIED
Issue or Number:13
PubMed Central ID:PMC3386217
Record Number:CaltechAUTHORS:20120807-121958516
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20120807-121958516
Official Citation:Mark S. Ladinsky, Kathryn E. Huey-Tubman, and Pamela J. Bjorkman Electron tomography of late stages of FcRn-mediated antibody transcytosis in neonatal rat small intestine Mol. Biol. Cell 2012 23:13 2537-2545; First Published on May 9, 2012; doi:10.1091/mbc.E12-02-0093
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:32983
Collection:CaltechAUTHORS
Deposited By: Aucoeur Ngo
Deposited On:07 Aug 2012 20:43
Last Modified:05 Nov 2019 21:26

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