T-cell antigen receptor-induced signaling complexes: internalization via a cholesterol-dependent endocytic pathway

Traffic. 2006 Sep;7(9):1143-62. doi: 10.1111/j.1600-0854.2006.00464.x.


T-cell antigen receptor engagement causes the rapid assembly of signaling complexes. The adapter protein SLP-76, detected as SLP-yellow fluorescent protein, initially clustered with the TCR and other proteins, then translocated medially on microtubules. As shown by total internal reflection fluorescence microscopy and the inhibition of SLP-76 movement at 16 degrees C, this movement required endocytosis. Immunoelectron microscopy showed SLP-76 staining of smooth pits and tubules. Cholesterol depletion decreased the movement of SLP-76 clusters, as did coexpression of the ubiquitin-interacting motif domain from eps15. These data are consistent with the internalization of SLP-76 via a lipid raft-dependent pathway that requires interaction of the endocytic machinery with ubiquitinylated proteins. The endocytosed SLP-76 clusters contained phosphorylated SLP-76 and phosphorylated LAT. The raft-associated, transmembrane protein LAT likely targets SLP-76 to endocytic vesicles. The endocytosis of active SLP-76 and LAT complexes suggests a possible mechanism for downregulation of signaling complexes induced by TCR activation.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism*
  • Cholesterol / physiology*
  • Endocytosis / physiology*
  • Humans
  • Phosphoproteins / metabolism*
  • Receptors, Antigen, T-Cell / physiology*
  • Signal Transduction / physiology*


  • Adaptor Proteins, Signal Transducing
  • Phosphoproteins
  • Receptors, Antigen, T-Cell
  • SLP-76 signal Transducing adaptor proteins
  • Cholesterol