A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains.
Partial complexes of the T cell antigen receptor lacking zeta chains are delivered to lysosomes. Chimeric proteins composed of the Tac antigen fused to the cytoplasmic domains of each CD3 chain has allowed the identification of lysosomal targeting sequences. Tac-gamma and Tac-delta chimeras are retained in the endoplasmic reticulum because of the presence of basic residues reminiscent of sequences responsible for the localization of endoplasmic reticulum resident proteins. Truncation of these retention motifs revealed lysosomal targeting of both Tac-gamma and delta chimeras. A di-leucine- and a tyrosine-based motif are individually sufficient to induce both endocytosis and delivery to lysosomes of Tac. In contrast with chimeras containing only one of these motifs, the chimera containing both was predominantly delivered directly to lysosomes without going through the cell surface. These two sequences may represent two families of targeting motifs that determine the fate of proteins within the peripheral membrane system.
Letourneur
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F
Cell Biology and Metabolism Branch, National Institute of Child Health, Human Development, National Institutes of Health, Bethesda, Maryland 20892.
Klausner
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RD
D000595:Amino Acid Sequence; D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism*; D017252:CD3 Complex; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D007930:Leucine; D008247:Lysosomes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D014443:Tyrosine
D000945:Antigens, Differentiation, T-Lymphocyte; D017252:CD3 Complex; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins; D014443:Tyrosine; D007930:Leucine