ArticlePloS one2013
Comparison of the intracellular trafficking itinerary of ctla-4 orthologues.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 16 citations in OpenAlex.
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Costimulatory receptors in the channel catfish: CD28 family members and their ligands.Immunogenetics · 2024Article
- Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates.Frontiers in immunology · 2024Article
- Regulation of CTLA-4 recycling by LRBA and Rab11.Immunology · 2021Article
- Treg-expressed CTLA-4 depletes CD80/CD86 by trogocytosis, releasing free PD-L1 on antigen-presenting cells.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- T cell receptor signaling defines the fate and pathway of ICOS internalization.Biochemistry and biophysics reports · 2020Article
- Molecular thermodynamics of receptor competition for endocytic uptake.Soft matter · 2019Article
- CTLA-4: a moving target in immunotherapy.Blood · 2018Review
- Confusing signals: recent progress in CTLA-4 biology.Trends in immunology · 2015Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.