The flotillins are integral membrane proteins in lipid rafts that contain TCR-associated signaling components: implications for T-cell activation.
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.
Slaughter
Ndaisha
N
Division of Clinical Immunology and Allergy, Department of Medicine, Los Angeles, CA 90095, USA.
Laux
Isett
I
Tu
Xiaolin
X
Whitelegge
Julian
J
Zhu
Xiaoming
X
Effros
Rita
R
Bickel
Perry
P
Nel
Andre
A
D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018106:CD28 Antigens / Q000494:pharmacology; D017252:CD3 Complex / Q000494:pharmacology; D002352:Carrier Proteins / Q000032:analysis / Q000378:metabolism; D006023:Glycoproteins / Q000032:analysis / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008213:Lymphocyte Activation; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000032:analysis / Q000378:metabolism; D021962:Membrane Microdomains / Q000737:chemistry*; D008565:Membrane Proteins / Q000032:analysis* / Q000378:metabolism; D010750:Phosphoproteins / Q000032:analysis; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D049231:Saposins; D015398:Signal Transduction; D049128:Sphingolipid Activator Proteins; D013601:T-Lymphocytes / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D018106:CD28 Antigens; D017252:CD3 Complex; D002352:Carrier Proteins; D006023:Glycoproteins; C110810:LAT protein, human; C491734:Lat protein, mouse; D008565:Membrane Proteins; C483345:PSAP protein, human; D010750:Phosphoproteins; C483344:Psap protein, mouse; D011948:Receptors, Antigen, T-Cell; D049231:Saposins; C402726:Sh2d2a protein, mouse; D049128:Sphingolipid Activator Proteins; C106354:flotillins; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)