title: The p55 tumour necrosis factor receptor TNFR1 contains a trans-Golgi network localization signal in the C-terminal region of its cytoplasmic tail.
abstract: It has been reported in some human cells that, in addition to a plasma membrane localization, members of the tumour necrosis factor receptor superfamily may be localized to the Golgi complex. We have shown by immunofluorescence and immunoelectron microscopy that the p55 tumour necrosis factor receptor, TNFR1, is principally localized to the trans-Golgi network in the human breast carcinoma cell line, MCF7. Chimaeras consisting of the extracellular and transmembrane domains of CD8 together with the cytoplasmic tail of TNFR1 were targeted to the trans-Golgi network in stably transfected rat fibroblastic cells. Deletions in the cytoplasmic tails of these chimaeras demonstrated the requirement for the C-terminal sequence of 23 amino acids for this targeting. The 23 amino acid sequence is mostly outside the death domain and contains both an acid patch and a dileucine motif. Interaction of this sequence with membrane traffic adaptor proteins may play an important role in controlling the responses of cells to tumour necrosis factor, since binding of signalling adaptor proteins has only been demonstrated for plasma membrane, and not Golgi-localized, TNFR1.
authors: Department of Clinical Biochemistry and Cambridge Institute for Medical Research, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2XY, U.K.
authors: Helen
authors: H
authors: Storey
authors: Abigail
authors: A
authors: Stewart
authors: Peter
authors: P
authors: Vandenabeele
authors: J Paul
authors: JP
authors: Luzio
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD / Q000737:chemistry* / Q000502:physiology*; D015153:Blotting, Western; D016827:CD8 Antigens / Q000096:biosynthesis; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006023:Glycoproteins; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry* / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D016827:CD8 Antigens; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D011500:Protein Synthesis Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; C072237:TGOLN2 protein, human; C513045:Tgoln2 protein, rat; D003513:Cycloheximide