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The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells
R. Roncagalli, M. Cucchetti, N. Jarmuzynski, C. Grégoire, E. Bergot, S. Audebert, E. Baudelet, MG. Menoita, A. Joachim, S. Durand, M. Suchanek, F. Fiore, L. Zhang, Y. Liang, L. Camoin, M. Malissen, B. Malissen,
Language English Country United States
Document type Journal Article
NLK
Free Medical Journals
from 1896 to 6 months ago
Europe PubMed Central
from 1896 to 6 months ago
Open Access Digital Library
from 1896-01-01
Open Access Digital Library
from 1896-01-01
Open Access Digital Library
from 1996-01-01
PubMed
27647348
DOI
10.1084/jem.20160579
Knihovny.cz E-resources
- MeSH
- Amino Acid Motifs MeSH
- CD28 Antigens metabolism MeSH
- Models, Biological MeSH
- Killer Cells, Natural metabolism MeSH
- Dendritic Cells metabolism MeSH
- Endocytosis MeSH
- Gene Targeting MeSH
- HEK293 Cells MeSH
- Jurkat Cells MeSH
- Humans MeSH
- Lymphocytes metabolism MeSH
- Protein Interaction Mapping MeSH
- Microfilament Proteins chemistry metabolism MeSH
- Protein Multimerization MeSH
- Mutation genetics MeSH
- Myeloid Cells metabolism MeSH
- Mice MeSH
- Protein Domains MeSH
- Proteomics MeSH
- T-Lymphocytes, Regulatory metabolism MeSH
- Signal Transduction MeSH
- T-Lymphocytes metabolism MeSH
- Thymocytes metabolism MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The RLTPR cytosolic protein, also known as CARMIL2, is essential for CD28 co-stimulation in mice, but its importance in human T cells and mode of action remain elusive. Here, using affinity purification followed by mass spectrometry analysis, we showed that RLTPR acts as a scaffold, bridging CD28 to the CARD11/CARMA1 cytosolic adaptor and to the NF-κB signaling pathway, and identified proteins not found before within the CD28 signaling pathway. We further demonstrated that RLTPR is essential for CD28 co-stimulation in human T cells and that its noncanonical pleckstrin-homology domain, leucine-rich repeat domain, and proline-rich region were mandatory for that task. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 co-stimulation in both mouse and human. Our findings suggest that the scaffolding role of RLTPR predominates during CD28 co-stimulation and underpins the similar function of RLTPR in human and mouse T cells. Along that line, the lack of functional RLTPR molecules impeded the differentiation toward Th1 and Th17 fates of both human and mouse CD4(+) T cells. RLTPR was also expressed in both human and mouse B cells. In the mouse, RLTPR did not play, however, any detectable role in BCR-mediated signaling and T cell-independent B cell responses.
Centre d'Immunologie de Marseille Luminy Aix Marseille Université INSERM CNRS 13288 Marseille France
Centre d'Immunophénomique Aix Marseille Université INSERM CNRS 13288 Marseille France
References provided by Crossref.org
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