Control of the intracellular pathway of CD1e.
CD1e is a membrane-associated protein predominantly detected in the Golgi compartments of immature human dendritic cells. Without transiting through the plasma membrane, it is targeted to lysosomes (Ls) where it remains as a cleaved and soluble form and participates in the processing of glycolipidic antigens. The role of the cytoplasmic tail of CD1e in the control of its intracellular pathway was studied. Experiments with chimeric molecules demonstrated that the cytoplasmic domain determines a cellular pathway that conditions the endosomal cleavage of these molecules. Other experiments showed that the C-terminal half of the cytoplasmic tail mediates the accumulation of CD1e in Golgi compartments. The cytoplasmic domain of CD1e undergoes monoubiquitinations, and its ubiquitination profile is maintained when its N- or C-terminal half is deleted. Replacement of the eight cytoplasmic lysines by arginines results in a marked accumulation of CD1e in trans Golgi network 46+ compartments, its expression on the plasma membrane and a moderate slowing of its transport to Ls. Fusion of this mutated form with ubiquitin abolishes the accumulation of CD1e molecules in the Golgi compartments and restores the kinetics of their transport to Ls. Thus, ubiquitination of CD1e appears to trigger its exit from Golgi compartments and its transport to endosomes. This ubiquitin-dependent pathway may explain several features of the very particular intracellular traffic of CD1e in dendritic cells compared with other CD1 molecules.
Maître
Blandine
B
INSERM, U725, Etablissement Français du Sang-Alsace, Strasbourg 67065, France, and Université Louis-Pasteur, Strasbourg 67000, France.
Angénieux
Catherine
C
Salamero
Jean
J
Hanau
Daniel
D
Fricker
Dominique
D
Signorino
François
F
Proamer
Fabienne
F
Cazenave
Jean-Pierre
JP
Goud
Bruno
B
Tourne
Sylvie
S
de la Salle
Henri
H
D000595:Amino Acid Sequence; D000818:Animals; D018949:Antigens, CD1 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D003713:Dendritic Cells / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D025801:Ubiquitin / Q000378:metabolism*
D018949:Antigens, CD1; C417738:CD1e antigen; D011993:Recombinant Fusion Proteins; D025801:Ubiquitin