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SNX17 Affects T Cell Activation by Regulating TCR and Integrin Recycling
Abstract
A key component in T cell activation is the endosomal recycling of receptors to the cell surface, thereby allowing continual integration of signaling and Ag recognition. One protein potentially involved in TCR transport is sorting nexin 17 (SNX17). SNX proteins have been found to bind proteins involved in T cell activation, but specifically the role of SNX17 in receptor recycling and T cell activation is unknown. Using immunofluorescence, we find that SNX17 colocalizes with TCR and localizes to the immune synapse in T– conjugates. Significantly, knockdown of the SNX17 resulted in fewer T–APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared with control T cells. Lastly, we identified the 4.1/ezrin/radixin/moesin domain of SNX17 as being responsible in the binding and trafficking of TCR and LFA-1 to the cell surface. These data suggest that SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse.
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SNX17 interacts with a multitude of receptors in a sequence-specific manner to regulate their recycling.
“Notably, SNX17 interacts with a multitude of receptors in a sequence-specific manner to regulate their recycling.”
From Sorting nexin 17 (SNX17) links endosomal sorting to Eps15 homology domain protein 1 (EHD1)–mediated fission machinery (2020) · cites this paper as [10]
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Endosomal retrieval of cargo: Retromer is not alone
McNally, K. E., & Cullen, P. J. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.06.005 · Cited by 169
Dhawan, K., Naslavsky, N., & Caplan, S. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra119.011368 · Cited by 36
Structural basis for Retriever-SNX17 assembly and endosomal sorting
Singla, A., Boesch, D. J., Fung, H. Y. J., Ngoka, C., Enriquez, A. S., Song, R., Kramer, D. A., Han, Y., Banarer, E., Lemoff, A., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-54583-6 · Cited by 23
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Metadata
- Authors
- Osborne, D. G., Piotrowski, J. T., Dick, C. J., Zhang, J.-S., & Billadeau, D. D.
- Affiliations
- Department of Immunology, Mayo Clinic College of Medicine , Rochester, MN 55905
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2015-05-01
- Volume
- 194
- Issue
- 9
- Pages
- 4555-4566
- ISSN
- 0022-1767
- 1550-6606
- PMC
- PMC4402276
- Cited by
- 50
- References
- 3
- Language
- en
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