The flotillins are integral membrane proteins in lipid rafts that contain TCR-associated signaling components: implications for T-cell activation
| Autor: | Perry E. Bickel, Ndaisha Slaughter, Xiaolin Tu, Andre E. Nel, Isett Laux, Xiaoming Zhu, Rita B. Effros, Julian P. Whitelegge |
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| Rok vydání: | 2003 |
| Předmět: |
Adult
Sphingolipid Activator Proteins CD3 Complex T-Lymphocytes T cell CD3 Immunology Receptors Antigen T-Cell Biology Lymphocyte Activation Jurkat cells Saposins Jurkat Cells Membrane Microdomains CD28 Antigens medicine Humans Immunology and Allergy Lipid raft Adaptor Proteins Signal Transducing Aged Glycoproteins Aged 80 and over T-cell receptor Membrane Proteins CD28 Raft Phosphoproteins Cell biology medicine.anatomical_structure Membrane protein Lymphocyte Specific Protein Tyrosine Kinase p56(lck) biology.protein lipids (amino acids peptides and proteins) Carrier Proteins Signal Transduction |
| Zdroj: | Clinical Immunology. 108:138-151 |
| ISSN: | 1521-6616 |
| DOI: | 10.1016/s1521-6616(03)00097-4 |
| Popis: | Lipid rafts play an important role in signal integration and cellular activation by the T-cell antigen receptor (TCR). We demonstrate that flotillin-1 and flotillin-2 are important structural raft components, which redistribute to the site of TCR engagement. An antibody to flotillin-1 was able to immobilize other TCR-associated raft components. Although rafts purified from unstimulated cells demonstrated abundant Lck but inabundant LAT, rafts from stimulated cells include an abundance of both components. This suggests dynamic changes in lipid raft composition during CD3/CD28 costimulation. Stimulation of primary human CD4(+) T cells leads to increased GM1 and flotillin-1 expression in the surface membrane, where these components colocalize. This may reconstitute new signaling complexes required for T-cell activation. Altered lipid raft composition and function may play a role in the decline of antigen responsiveness in senescent T cells. In this regard, we observed an increase in the raft-associated gangliolipid, GM1, in resting human CD4(+) and CD8(+) lymphocytes with aging. |
| Databáze: | OpenAIRE |
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