SORA

Advancing, promoting and sharing knowledge of health through excellence in teaching, clinical practice and research into the prevention and treatment of illness

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

Kaur, S; Qureshi, OS; Sansom, DM (2013) Comparison of the intracellular trafficking itinerary of ctla-4 orthologues. PLoS One, 8 (4). e60903. ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0060903
SGUL Authors: Kaur, Satdip

[img]
Preview
PDF Accepted Version
Available under License Creative Commons Attribution.

Download (2MB) | Preview

Abstract

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.

Item Type: Article
Additional Information: © 2013 Kaur et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Animals, CTLA-4 Antigen, Chickens, Endocytosis, Humans, Protein Transport, Signal Transduction, Trout, Xenopus, Animals, Xenopus, Chickens, Trout, Humans, Signal Transduction, Endocytosis, Protein Transport, CTLA-4 Antigen, General Science & Technology, MD Multidisciplinary
SGUL Research Institute / Research Centre: Academic Structure > Molecular and Clinical Sciences Research Institute (MCS)
Journal or Publication Title: PLoS One
ISSN: 1932-6203
Language: eng
Dates:
DateEvent
2 April 2013Published
5 March 2013Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
BB/H013598/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
UNSPECIFIEDBiotechnology and Biological Sciences Research CouncilUNSPECIFIED
PubMed ID: 23565286
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109811
Publisher's version: https://doi.org/10.1371/journal.pone.0060903

Actions (login required)

Edit Item Edit Item