The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Constitutive Clathrin-mediated Endocytosis of CTLA-4 Persists during T Cell Activation
Open accessAbstract
CTLA-4 is one of the most important negative regulators of the T cell immune response. However, the subcellular distribution of CTLA-4 is unusual for a receptor that interacts with cell surface transmembrane ligands in that CTLA-4 is rapidly internalized from the plasma membrane. It has been proposed that T cell activation can lead to stabilization of CTLA-4 expression at the cell surface. Here we have analyzed in detail the internalization, recycling, and degradation of CTLA-4. We demonstrate that CTLA-4 is rapidly internalized from the plasma membrane in a clathrin- and dynamin-dependent manner driven by the well characterized YVKM trafficking motif. Furthermore, we show that once internalized, CTLA-4 co-localizes with markers of recycling endosomes and is recycled to the plasma membrane. Although we observed limited co-localization of CTLA-4 with lysosomal markers, CTLA-4 was nonetheless degraded in a manner inhibited by lysosomal blockade. T cell activation stimulated mobilization of CTLA-4, as judged by an increase in cell surface expression; however, this pool of CTLA-4 continued to endocytose and was not stably retained at the cell surface. These data support a model of trafficking whereby CTLA-4 is constitutively internalized in a ligand-independent manner undergoing both recycling and degradation. Stimulation of T cells increases CTLA-4 turnover at the plasma membrane; however, CTLA-4 endocytosis continues and is not stabilized during activation of human T cells. These findings emphasize the importance of clathrin-mediated endocytosis in regulating CTLA-4 trafficking throughout T cell activation.
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Cites
Doherty, G. J., & McMahon, H. T. (2009) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.78.081307.110540 · Cited by 3,075
Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4
Waterhouse, P., Penninger, J. M., Timms, E., Wakeham, A., Shahinian, A., Lee, K. P., Thompson, C. B., Griesser, H., & Mak, T. W. (1995) · Science · doi:10.1126/science.270.5238.985 · Cited by 2,766
Trans-endocytosis of CD80 and CD86: a molecular basis for the cell-extrinsic function of CTLA-4
Qureshi, O. S., Zheng, Y., Nakamura, K., Attridge, K., Manzotti, C., Schmidt, E. M., Baker, J., Jeffery, L. E., Kaur, S., Briggs, Z., et al. (2011) · Science · doi:10.1126/science.1202947 · Cited by 1,860 · cited 4×
“The purpose of recycling of CTLA-4 is unknown; however, recently we have shown that one function of CTLA-4 is its ability to remove ligands from antigen-presenting cells (8).”
BackgroundMethodInfluentialSelf-citationRegulation of Cytotoxic T Lymphocyte-Associated Molecule-4 by Src Kinases
Chuang, E., Lee, K.-M., Robbins, M. D., Duerr, J. M., Alegre, M.-L., Hambor, J. E., Neveu, M. J., Bluestone, J. A., & Thompson, C. B. (1999) · The Journal of Immunology · doi:10.4049/jimmunol.162.3.1270 · Cited by 119
Src Family Tyrosine Kinases Associate with and Phosphorylate CTLA-4 (CD152)
Miyatake, S., Nakaseko, C., Umemori, H., Yamamoto, T., & Saito, T. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1998.9191 · Cited by 65
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Rowshanravan, B., Halliday, N., & Sansom, D. M. (2018) · Blood · doi:10.1182/blood-2017-06-741033 · Cited by 1,233
Self-citationTekguc, M., Wing, J. B., Osaki, M., Long, J., & Sakaguchi, S. (2021) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2023739118 · Cited by 490
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Metadata
- Authors
- Qureshi, O. S., Kaur, S., Hou, T. Z., Jeffery, L. E., Poulter, N. S., Briggs, Z., Kenefeck, R., Willox, A. K., Royle, S. J., Rappoport, J. Z., & Sansom, D. M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-03
- Volume
- 287
- Issue
- 12
- Pages
- 9429-9440
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W1996217426
- Cited by
- 172
- References
- 5
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Qureshi, O. S., Kaur, S., Hou, T. Z., Jeffery, L. E., Poulter, N. S., Briggs, Z., Kenefeck, R., Willox, A. K., Royle, S. J., Rappoport, J. Z., & Sansom, D. M. (2012). Constitutive Clathrin-mediated Endocytosis of CTLA-4 Persists during T Cell Activation. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m111.304329
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