Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.

<h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET fa...

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Autores principales:	Robert A Eagle, Gillian Flack, Anthony Warford, Jesús Martínez-Borra, Insiya Jafferji, James A Traherne, Maki Ohashi, Louise H Boyle, Alexander D Barrow, Sophie Caillat-Zucman, Neil T Young, John Trowsdale
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fc713ba0efb440538c1dc3d4584813bd
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spelling	oai:doaj.org-article:fc713ba0efb440538c1dc3d4584813bd2021-12-02T20:12:16ZCellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.1932-620310.1371/journal.pone.0004503https://doaj.org/article/fc713ba0efb440538c1dc3d4584813bd2009-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19223974/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised.<h4>Methodology/principal findings</h4>We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy.<h4>Conclusions/significance</h4>We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality.Robert A EagleGillian FlackAnthony WarfordJesús Martínez-BorraInsiya JafferjiJames A TraherneMaki OhashiLouise H BoyleAlexander D BarrowSophie Caillat-ZucmanNeil T YoungJohn TrowsdalePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 4, Iss 2, p e4503 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
description	<h4>Background</h4>The activating immunoreceptor NKG2D is expressed on Natural Killer (NK) cells and subsets of T cells. NKG2D contributes to anti-tumour and anti-viral immune responses in vitro and in vivo. The ligands for NKG2D in humans are diverse proteins of the MIC and ULBP/RAET families that are upregulated on the surface of virally infected cells and tumours. Two splicing variants of ULBP5/RAET1G have been cloned previously, but not extensively characterised.<h4>Methodology/principal findings</h4>We pursue a number of approaches to characterise the expression, trafficking, and function of the two isoforms of ULBP5/RAET1G. We show that both transcripts are frequently expressed in cell lines derived from epithelial cancers, and in primary breast cancers. The full-length transcript, RAET1G1, is predicted to encode a molecule with transmembrane and cytoplasmic domains that are unique amongst NKG2D ligands. Using specific anti-RAET1G1 antiserum to stain tissue microarrays we show that RAET1G1 expression is highly restricted in normal tissues. RAET1G1 was expressed at a low level in normal gastrointestinal epithelial cells in a similar pattern to MICA. Both RAET1G1 and MICA showed increased expression in the gut of patients with celiac disease. In contrast to healthy tissues the RAET1G1 antiserum stained a wide variety or different primary tumour sections. Both endogenously expressed and transfected RAET1G1 was mainly found inside the cell, with a minority of the protein reaching the cell surface. Conversely the truncated splicing variant of RAET1G2 was shown to encode a soluble molecule that could be secreted from cells. Secreted RAET1G2 was shown to downregulate NKG2D receptor expression on NK cells and hence may represent a novel tumour immune evasion strategy.<h4>Conclusions/significance</h4>We demonstrate that the expression patterns of ULBP5RAET1G are very similar to the well-characterised NKG2D ligand, MICA. However the two isoforms of ULBP5/RAET1G have very different cellular localisations that are likely to reflect unique functionality.
format	article
author	Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale
author_facet	Robert A Eagle Gillian Flack Anthony Warford Jesús Martínez-Borra Insiya Jafferji James A Traherne Maki Ohashi Louise H Boyle Alexander D Barrow Sophie Caillat-Zucman Neil T Young John Trowsdale
author_sort	Robert A Eagle
title	Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
title_short	Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
title_full	Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
title_fullStr	Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
title_full_unstemmed	Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.
title_sort	cellular expression, trafficking, and function of two isoforms of human ulbp5/raet1g.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/fc713ba0efb440538c1dc3d4584813bd
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Cellular expression, trafficking, and function of two isoforms of human ULBP5/RAET1G.

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