A role for the cytoplasmic tail of the pre-T cell receptor (TCR) alpha chain in promoting constitutive internalization and degradation of the pre-TCR.
Engagement of the alpha beta T cell receptor (TCR) by its ligand results in the down-modulation of TCR cell surface expression, which is thought to be a central event in T cell activation. On the other hand, pre-TCR signaling is a key process in alpha beta T cell development, which appears to proceed in a constitutive and ligand-independent manner. Here, comparative analyses on the dynamics of pre-TCR and TCR cell surface expression show that unligated pre-TCR complexes expressed on human pre-T cells behave as engaged TCR complexes, i.e. they are rapidly internalized and degraded in lysosomes and proteasomes but do not recycle back to the cell surface. Thus, pre-TCR down-regulation takes place constitutively without the need for extracellular ligation. By using TCR alpha/p Tau alpha chain chimeras, we demonstrate that prevention of recycling and induction of degradation are unique pre-TCR properties conferred by the cytoplasmic domain of the pT alpha chain. Finally, we show that pre-TCR internalization is a protein kinase C-independent process that involves the combination of src kinase-dependent and -independent pathways. These data suggest that constitutive pre-TCR down-modulation regulates pre-TCR surface expression levels and hence the extent of ligand-independent signaling through the pre-TCR.
Carrasco
Yolanda R
YR
Centro de Biologia Molecular Severo Ochoa, Consejo Superior de Investigaciones Cientificas, Facultad de Biologia, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Navarro
Maria N
MN
Toribio
María L
ML
D019921:Biotinylation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D019281:Dimerization; D015536:Down-Regulation; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D008024:Ligands; D008164:Luminescent Proteins / Q000378:metabolism; D008247:Lysosomes / Q000378:metabolism; D018613:Microscopy, Confocal; D011233:Precipitin Tests; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry* / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
D008024:Ligands; D008164:Luminescent Proteins; D011948:Receptors, Antigen, T-Cell; D049452:Green Fluorescent Proteins; D011493:Protein Kinase C