Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.

CTLA-4 is an essential inhibitor of T cell immune responses. At steady state, most CTLA-4 resides in intracellular compartments due to constitutive internalisation mediated via a tyrosine based endocytic motif (YVKM) within the cytoplasmic domain. This domain is highly conserved in mammals suggestin...

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Autores principales:	Satdip Kaur, Omar S Qureshi, David M Sansom
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1ef725d233644bab8bd4321dc2e67a55
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spelling	oai:doaj.org-article:1ef725d233644bab8bd4321dc2e67a552021-11-18T07:50:53ZComparison of the intracellular trafficking itinerary of ctla-4 orthologues.1932-620310.1371/journal.pone.0060903https://doaj.org/article/1ef725d233644bab8bd4321dc2e67a552013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23565286/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203CTLA-4 is an essential inhibitor of T cell immune responses. At steady state, most CTLA-4 resides in intracellular compartments due to constitutive internalisation mediated via a tyrosine based endocytic motif (YVKM) within the cytoplasmic domain. This domain is highly conserved in mammals suggesting strong selective pressure. In contrast, the C-terminal domain varies considerably in non-mammals such as fish, xenopus and birds. We compared the ability of the C-terminus of these species to direct the trafficking of CTLA-4 with human CTLA-4. Using a chimeric approach, endocytosis was found to be conserved between human, xenopus and chicken CTLA-4 but was reduced substantially in trout CTLA-4, which lacks the conserved YXXM motif. Nevertheless, we identified an alternative YXXF motif in trout CTLA-4 that permitted limited endocytosis. Post-internalisation, CTLA-4 was either recycled or targeted for degradation. Human and chicken CTLA-4, which contain a YVKM motif, showed efficient recycling compared to xenopus CTLA-4 which contains a less efficient YEKM motif. Specific mutation of this motif in human CTLA-4 reduced receptor recycling. These findings suggest evolutionary development in the endocytic and recycling potential of CTLA-4, which may facilitate more refined functions of CTLA-4 within the mammalian immune system.Satdip KaurOmar S QureshiDavid M SansomPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 4, p e60903 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Satdip Kaur Omar S Qureshi David M Sansom Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
description	CTLA-4 is an essential inhibitor of T cell immune responses. At steady state, most CTLA-4 resides in intracellular compartments due to constitutive internalisation mediated via a tyrosine based endocytic motif (YVKM) within the cytoplasmic domain. This domain is highly conserved in mammals suggesting strong selective pressure. In contrast, the C-terminal domain varies considerably in non-mammals such as fish, xenopus and birds. We compared the ability of the C-terminus of these species to direct the trafficking of CTLA-4 with human CTLA-4. Using a chimeric approach, endocytosis was found to be conserved between human, xenopus and chicken CTLA-4 but was reduced substantially in trout CTLA-4, which lacks the conserved YXXM motif. Nevertheless, we identified an alternative YXXF motif in trout CTLA-4 that permitted limited endocytosis. Post-internalisation, CTLA-4 was either recycled or targeted for degradation. Human and chicken CTLA-4, which contain a YVKM motif, showed efficient recycling compared to xenopus CTLA-4 which contains a less efficient YEKM motif. Specific mutation of this motif in human CTLA-4 reduced receptor recycling. These findings suggest evolutionary development in the endocytic and recycling potential of CTLA-4, which may facilitate more refined functions of CTLA-4 within the mammalian immune system.
format	article
author	Satdip Kaur Omar S Qureshi David M Sansom
author_facet	Satdip Kaur Omar S Qureshi David M Sansom
author_sort	Satdip Kaur
title	Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
title_short	Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
title_full	Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
title_fullStr	Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
title_full_unstemmed	Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
title_sort	comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/1ef725d233644bab8bd4321dc2e67a55
work_keys_str_mv	AT satdipkaur comparisonoftheintracellulartraffickingitineraryofctla4orthologues AT omarsqureshi comparisonoftheintracellulartraffickingitineraryofctla4orthologues AT davidmsansom comparisonoftheintracellulartraffickingitineraryofctla4orthologues
_version_	1718422838649552896

Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.

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