The cytoplasmic domain mediates localization of furin to the trans- Golgi network en route to the endosomal/lysosomal system

doi:10.1083/jcb.126.5.1157

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The cytoplasmic domain mediates localization of furin to the trans- Golgi network en route to the endosomal/lysosomal system

H Bosshart, J Humphrey, E Deignan, J Davidson, J Drazba, L Yuan, V Oorschot, PJ Peters and JS Bonifacino
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892.

To investigate the mechanisms of membrane protein localization to the Golgi complex, we have examined the intracellular trafficking of epitope-tagged forms of the mammalian endopeptidase, furin, in stably transformed rat basophilic leukemia cells. Our studies show that furin is predominantly localized to the trans-Golgi network (TGN) at steady state, with smaller amounts present in intracellular vesicles. Biochemical and morphological analyses reveal that furin is progressively delivered to a lysosomal compartment, where it is degraded. Analyses of furin deletion mutants and chimeric proteins show that the cytoplasmic domain is both necessary and sufficient for localization to the TGN in various cell types. Interestingly, deletion of most of the cytoplasmic domain of furin results in a molecule that is predominantly localized to intracellular vesicles, some of which display characteristics of lysosomes. To a lesser extent, the cytoplasmically deleted molecule is also localized to the plasma membrane. These observations suggest the existence of an additional determinant for targeting to the endosomal/lysosomal system within the lumenal and/or transmembrane domains of furin. Thus, the overall pattern of trafficking and steady state localization of furin are determined by targeting information contained within more than one region of the molecule.
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White, C. L., Weisberg, A. S., Moss, B. (2000). A Glutaredoxin, Encoded by the G4L Gene of Vaccinia Virus, Is Essential for Virion Morphogenesis. J. Virol. 74: 9175-9183 [Abstract] [Full Text]
Berson, J. F., Frank, D. W., Calvo, P. A., Bieler, B. M., Marks, M. S. (2000). A Common Temperature-sensitive Allelic Form of Human Tyrosinase Is Retained in the Endoplasmic Reticulum at the Nonpermissive Temperature. J. Biol. Chem. 275: 12281-12289 [Abstract] [Full Text]
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Subtil, A., Lampson, M. A, Keller, S. R., McGraw, T. E. (2000). Characterization of the Insulin-regulated Endocytic Recycling Mechanism in 3T3-L1 Adipocytes Using a Novel Reporter Molecule. J. Biol. Chem. 275: 4787-4795 [Abstract] [Full Text]
Teuchert, M., Berghofer, S., Klenk, H.-D., Garten, W. (1999). Recycling of Furin from the Plasma Membrane. FUNCTIONAL IMPORTANCE OF THE CYTOPLASMIC TAIL SORTING SIGNALS AND INTERACTION WITH THE AP-2 ADAPTOR MEDIUM CHAIN SUBUNIT. J. Biol. Chem. 274: 36781-36789 [Abstract] [Full Text]
Puertollano, R., Alonso, M. A. (1999). MAL, an Integral Element of the Apical Sorting Machinery, Is an Itinerant Protein That Cycles between the Trans-Golgi Network and the Plasma Membrane. Mol. Biol. Cell 10: 3435-3447 [Abstract] [Full Text]
Bruzzaniti, A., Marx, R., Mains, R. E. (1999). Activation and Routing of Membrane-tethered Prohormone Convertases 1 and 2. J. Biol. Chem. 274: 24703-24713 [Abstract] [Full Text]
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Brideau, A. D., del Rio, T., Wolffe, E. J., Enquist, L. W. (1999). Intracellular Trafficking and Localization of the Pseudorabies Virus Us9 Type II Envelope Protein to Host and Viral Membranes. J. Virol. 73: 4372-4384 [Abstract] [Full Text]
Simmen, T., Nobile, M., Bonifacino, J. S., Hunziker, W. (1999). Basolateral Sorting of Furin in MDCK Cells Requires a Phenylalanine-Isoleucine Motif Together with an Acidic Amino Acid Cluster. Mol. Cell. Biol. 19: 3136-3144 [Abstract] [Full Text]
Thacker, C., Marra, M. A., Jones, A., Baillie, D. L., Rose, A. M. (1999). Functional Genomics in Caenorhabditis elegans: An Approach Involving Comparisons of Sequences from Related Nematodes. Genome Res 9: 348-359 [Abstract] [Full Text]
Teuchert, M., Schafer, W., Berghofer, S., Hoflack, B., Klenk, H.-D., Garten, W. (1999). Sorting of Furin at the Trans-Golgi Network. INTERACTION OF THE CYTOPLASMIC TAIL SORTING SIGNALS WITH AP-1 GOLGI-SPECIFIC ASSEMBLY PROTEINS. J. Biol. Chem. 274: 8199-8207 [Abstract] [Full Text]
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Leclerc, D., Chapdelaine, Y., Hohn, T. (1999). Nuclear Targeting of the Cauliflower Mosaic Virus Coat Protein. J. Virol. 73: 553-560 [Abstract] [Full Text]
Eng, F. J., Varlamov, O., Fricker, L. D. (1999). Sequences within the Cytoplasmic Domain of Gp180/Carboxypeptidase D Mediate Localization to the Trans-Golgi Network. Mol. Biol. Cell 10: 35-46 [Abstract] [Full Text]
Andersson, A. M., Pettersson, R. F. (1998). Targeting of a Short Peptide Derived from the Cytoplasmic Tail of the G1 Membrane Glycoprotein of Uukuniemi Virus (Bunyaviridae) to the Golgi Complex. J. Virol. 72: 9585-9596 [Abstract] [Full Text]
Molloy, S. S., Thomas, L., Kamibayashi, C., Mumby, M. C., Thomas, G. (1998). Regulation of Endosome Sorting by a Specific PP2A Isoform. JCB 142: 1399-1411 [Abstract] [Full Text]
Tugizov, S., Maidji, E., Xiao, J., Zheng, Z., Pereira, L. (1998). Human Cytomegalovirus Glycoprotein B Contains Autonomous Determinants for Vectorial Targeting to Apical Membranes of Polarized Epithelial Cells. J. Virol. 72: 7374-7386 [Abstract] [Full Text]
Ghosh, R. N., Mallet, W. G., Soe, T. T., McGraw, T. E., Maxfield, F. R. (1998). An Endocytosed TGN38 Chimeric Protein Is Delivered to the TGN after Trafficking through the Endocytic Recycling Compartment in CHO Cells. JCB 142: 923-936 [Abstract] [Full Text]
Claus, V., Jahraus, A., Tjelle, T., Berg, T., Kirschke, H., Faulstich, H., Griffiths, G. (1998). Lysosomal Enzyme Trafficking between Phagosomes, Endosomes, and Lysosomes in J774 Macrophages. ENRICHMENT OF CATHEPSIN H IN EARLY ENDOSOMES. J. Biol. Chem. 273: 9842-9851 [Abstract] [Full Text]
Demaurex, N., Furuya, W., D'Souza, S., Bonifacino, J. S., Grinstein, S. (1998). Mechanism of Acidification of the trans-Golgi Network (TGN). IN SITU MEASUREMENTS OF pH USING RETRIEVAL OF TGN38 AND FURIN FROM THE CELL SURFACE. J. Biol. Chem. 273: 2044-2051 [Abstract] [Full Text]
Cole, N. B., Ellenberg, J., Song, J., DiEuliis, D., Lippincott-Schwartz, J. (1998). Retrograde Transport of Golgi-localized Proteins to the ER. JCB 140: 1-15 [Abstract] [Full Text]
Varlamov, O, Fricker, L. (1998). Intracellular trafficking of metallocarboxypeptidase D in AtT-20 cells: localization to the trans-Golgi network and recycling from the cell surface. J. Cell Sci. 111: 877-885 [Abstract]
Wolins, N., Bosshart, H., Kuster, H., Bonifacino, J. S. (1997). Aggregation As a Determinant of Protein Fate in Post-Golgi Compartments: Role of the Luminal Domain of Furin in Lysosomal Targeting. JCB 139: 1735-1745 [Abstract] [Full Text]
van de Loo, J.-W. H.�P., Creemers, J. W.�M., Bright, N. A., Young, B. D., Roebroek, A. J.�M., Van de Ven, W. J.�M. (1997). Biosynthesis, Distinct Post-translational Modifications, and Functional Characterization of Lymphoma Proprotein Convertase. J. Biol. Chem. 272: 27116-27123 [Abstract] [Full Text]
Benjannet, S., Savaria, D., Laslop, A., Munzer, J. S., Chretien, M., Marcinkiewicz, M., Seidah, N. G. (1997). alpha 1-Antitrypsin Portland Inhibits Processing of Precursors Mediated by Proprotein Convertases Primarily within the Constitutive Secretory Pathway. J. Biol. Chem. 272: 26210-26218 [Abstract] [Full Text]
Yuan, D. S., Dancis, A., Klausner, R. D. (1997). Restriction of Copper Export in Saccharomyces cerevisiae to a Late Golgi or Post-Golgi Compartment in the Secretory Pathway. J. Biol. Chem. 272: 25787-25793 [Abstract] [Full Text]
Brickner, J. H., Fuller, R. S. (1997). SOI1 Encodes a Novel, Conserved Protein That Promotes TGN-Endosomal Cycling of Kex2p and Other Membrane Proteins by Modulating the Function of Two TGN Localization Signals. JCB 139: 23-36 [Abstract] [Full Text]
Sawada, Y., Suda, M., Yokoyama, H., Kanda, T., Sakamaki, T., Tanaka, S., Nagai, R., Abe, S., Takeuchi, T. (1997). Stretch-induced Hypertrophic Growth of Cardiocytes and Processing of Brain-type Natriuretic Peptide Are Controlled by Proprotein-processing Endoprotease Furin. J. Biol. Chem. 272: 20545-20554 [Abstract] [Full Text]
Hatakeyama, S., Jensen, J. P., Weissman, A. M. (1997). Subcellular Localization and Ubiquitin-conjugating Enzyme (E2) Interactions of Mammalian HECT Family Ubiquitin Protein Ligases. J. Biol. Chem. 272: 15085-15092 [Abstract] [Full Text]
Yang, M., Ellenberg, J., Bonifacino, J. S., Weissman, A. M. (1997). The Transmembrane Domain of a Carboxyl-terminal Anchored Protein Determines Localization to the Endoplasmic Reticulum. J. Biol. Chem. 272: 1970-1975 [Abstract] [Full Text]
Shapiro, J., Sciaky, N., Lee, J., Bosshart, H., Angeletti, R. H., Bonifacino, J. S. (1997). Localization of Endogenous Furin in Cultured Cell Lines. J. Histochem. Cytochem. 45: 3-12 [Abstract] [Full Text]
Klumperman, J., Spijker, S., van Minnen, J., Sharp-Baker, H., Smit, A. B., Geraerts, W. P.�M. (1996). Cell Type-Specific Sorting of Neuropeptides: A Mechanism to Modulate Peptide Composition of Large Dense-Core Vesicles. J. Neurosci. 16: 7930-7940 [Abstract] [Full Text]
Creemers, J. W.M., Usac, E. F., Bright, N. A., Van de Loo, J.-W., Jansen, E., Van de Ven, W. J.M., Hutton, J. C. (1996). Identification of a Transferable Sorting Domain for the Regulated Pathway in the Prohormone Convertase PC2. J. Biol. Chem. 271: 25284-25291 [Abstract] [Full Text]
Milgram, S. L., Mains, R. E., Eipper, B. A. (1996). Identification of Routing Determinants in the Cytosolic Domain of a Secretory Granule-associated Integral Membrane Protein. J. Biol. Chem. 271: 17526-17535 [Abstract] [Full Text]
Kayo, T., Sawada, Y., Suzuki, Y., Suda, M., Tanaka, S., Konda, Y., Miyazaki, J.-i., Takeuchi, T. (1996). Proprotein-processing Endoprotease Furin Decreases Regulated Secretory Pathway-specific Proteins in the Pancreatic beta Cell Line MIN6. J. Biol. Chem. 271: 10731-10737 [Abstract] [Full Text]
Ralston, E, Ploug, T (1996). GLUT4 in cultured skeletal myotubes is segregated from the transferrin receptor and stored in vesicles associated with TGN. J. Cell Sci. 109: 2967-2978 [Abstract]
Takahashi, S., Nakagawa, T., Banno, T., Watanabe, T., Murakami, K., Nakayama, K. (1995). Localization of Furin to the trans-Golgi Network and Recycling from the Cell Surface Involves Ser and Tyr Residues within the Cytoplasmic Domain. J. Biol. Chem. 270: 28397-28401 [Abstract] [Full Text]
Garred, , Deurs, B. v., Sandvig, K. (1995). Furin-induced Cleavage and Activation of Shiga Toxin. J. Biol. Chem. 270: 10817-10821 [Abstract] [Full Text]
Franzusoff, A., Volpe, A. M., Josse, D., Pichuantes, S., Wolf, J. R. (1995). Biochemical and Genetic Definition of the Cellular Protease Required for HIV-1 gp160 Processing. J. Biol. Chem. 270: 3154-3159 [Abstract] [Full Text]
Sariola, M, Saraste, J, Kuismanen, E (1995). Communication of post-Golgi elements with early endocytic pathway: regulation of endoproteolytic cleavage of Semliki Forest virus p62 precursor. J. Cell Sci. 108: 2465-2475 [Abstract]
Krise, J. P., Sincock, P. M., Orsel, J. G., Pfeffer, S. R. (2000). Quantitative Analysis of TIP47-Receptor Cytoplasmic Domain Interactions. IMPLICATIONS FOR ENDOSOME-TO-TRANS GOLGI NETWORK TRAFFICKING. J. Biol. Chem. 275: 25188-25193 [Abstract] [Full Text]
Phillips, S. A., Barr, V. A., Haft, D. H., Taylor, S. I., Haft, C. R. (2001). Identification and Characterization of SNX15, a Novel Sorting Nexin Involved in Protein Trafficking. J. Biol. Chem. 276: 5074-5084 [Abstract] [Full Text]