Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)

Abstract Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular tra...

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Autores principales:	R. B. Cejas, M. Tamaño-Blanco, J. G. Blanco
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/be4f6891f9b243299f18303bb9458488
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spelling	oai:doaj.org-article:be4f6891f9b243299f18303bb94584882021-12-02T14:42:00ZAnalysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)10.1038/s41598-021-90469-z2045-2322https://doaj.org/article/be4f6891f9b243299f18303bb94584882021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90469-zhttps://doaj.org/toc/2045-2322Abstract Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular traffic of IgG mediated by the human neonatal Fc receptor (FcRn) in fibroblast cell lines with trisomy 21. Intracellular IgG trafficking studies in live cells showed that fibroblasts with trisomy 21 exhibit higher proportion of IgG in lysosomes (~ 10% increase), decreased IgG content in intracellular vesicles (~ 9% decrease), and a trend towards decreased IgG recycling (~ 55% decrease) in comparison to diploid cells. Amyloid-beta precursor protein (APP) overexpression in diploid fibroblasts replicated the increase in IgG sorting to the degradative pathway observed in cells with trisomy 21. The impact of APP on the expression of FCGRT (alpha chain component of FcRn) was investigated by APP knock down and overexpression of the APP protein. APP knock down increased the expression of FCGRT mRNA by ~ 60% in both diploid and trisomic cells. Overexpression of APP in diploid fibroblasts and HepG2 cells resulted in a decrease in FCGRT and FcRn expression. Our results indicate that the intracellular traffic of IgG is altered in cells with trisomy 21. This study lays the foundation for future investigations into the role of FcRn in the context of DS.R. B. CejasM. Tamaño-BlancoJ. G. BlancoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q R. B. Cejas M. Tamaño-Blanco J. G. Blanco Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
description	Abstract Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular traffic of IgG mediated by the human neonatal Fc receptor (FcRn) in fibroblast cell lines with trisomy 21. Intracellular IgG trafficking studies in live cells showed that fibroblasts with trisomy 21 exhibit higher proportion of IgG in lysosomes (~ 10% increase), decreased IgG content in intracellular vesicles (~ 9% decrease), and a trend towards decreased IgG recycling (~ 55% decrease) in comparison to diploid cells. Amyloid-beta precursor protein (APP) overexpression in diploid fibroblasts replicated the increase in IgG sorting to the degradative pathway observed in cells with trisomy 21. The impact of APP on the expression of FCGRT (alpha chain component of FcRn) was investigated by APP knock down and overexpression of the APP protein. APP knock down increased the expression of FCGRT mRNA by ~ 60% in both diploid and trisomic cells. Overexpression of APP in diploid fibroblasts and HepG2 cells resulted in a decrease in FCGRT and FcRn expression. Our results indicate that the intracellular traffic of IgG is altered in cells with trisomy 21. This study lays the foundation for future investigations into the role of FcRn in the context of DS.
format	article
author	R. B. Cejas M. Tamaño-Blanco J. G. Blanco
author_facet	R. B. Cejas M. Tamaño-Blanco J. G. Blanco
author_sort	R. B. Cejas
title	Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
title_short	Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
title_full	Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
title_fullStr	Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
title_full_unstemmed	Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)
title_sort	analysis of the intracellular traffic of igg in the context of down syndrome (trisomy 21)
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/be4f6891f9b243299f18303bb9458488
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Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)

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