Unknown

Dataset Information

0

Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation.


ABSTRACT: 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.

SUBMITTER: Qureshi OS 

PROVIDER: S-EPMC3308817 | biostudies-other | 2012 Mar

REPOSITORIES: biostudies-other

altmetric image

Publications

Constitutive clathrin-mediated endocytosis of CTLA-4 persists during T cell activation.

Qureshi Omar S OS   Kaur Satdip S   Hou Tie Zheng TZ   Jeffery Louisa E LE   Poulter Natalie S NS   Briggs Zoe Z   Kenefeck Rupert R   Willox Anna K AK   Royle Stephen J SJ   Rappoport Joshua Z JZ   Sansom David M DM  

The Journal of biological chemistry 20120119 12


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 t  ...[more]

Similar Datasets

| S-EPMC3849811 | biostudies-literature
| S-EPMC3340072 | biostudies-literature
| S-EPMC6526708 | biostudies-literature
| S-EPMC3167020 | biostudies-literature
| S-EPMC4309520 | biostudies-literature
| S-EPMC5223608 | biostudies-literature
| S-EPMC5702056 | biostudies-literature
| S-EPMC3115502 | biostudies-literature
| S-EPMC6928437 | biostudies-literature
| S-EPMC4050722 | biostudies-literature