Home LiteratureArticle Details
PMID: 10082580 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Basolateral sorting of furin in MDCK cells requires a phenylalanine-isoleucine motif together with an acidic amino acid cluster.

Molecular and cellular biology ·Vol. 19 ·No. 4 ·1999-04-00 ·Pages 3136-44

Simmen T, Nobile M, Bonifacino JS, Hunziker W

Abstract

Furin is a subtilisin-related endoprotease which processes a wide range of bioactive proteins. Furin is concentrated in the trans-Golgi network (TGN), where proteolytic activation of many precursor proteins takes place. A significant fraction of furin, however, cycles among the TGN, the plasma membrane, and endosomes, indicating that the accumulation in the TGN reflects a dynamic localization process. The cytosolic domain of furin is necessary and sufficient for TGN localization, and two signals are responsible for retrieval of furin to the TGN. A tyrosine-based (YKGL) motif mediates internalization of furin from the cell surface into endosomes. An acidic cluster that is part of two casein kinase II phosphorylation sites (SDSEEDE) is then responsible for retrieval of furin from endosomes to the TGN. In addition, the acidic EEDE sequence also mediates endocytic activity. Here, we analyzed the sorting of furin in polarized epithelial cells. We show that furin is delivered to the basolateral surface of MDCK cells, from where a significant fraction of the protein can return to the TGN. A phenylalanine-isoleucine motif together with the acidic EEDE cluster is required for basolateral sorting and constitutes a novel signal regulating intracellular traffic of furin.

MeSH Terms
Amino Acid Sequence Amino Acids, Dicarboxylic Animals Biological Transport Cell Compartmentation Cell Membrane/metabolism Cell Polarity/physiology Dogs Endosomes/metabolism Epithelial Cells/cytology Furin Golgi Apparatus/metabolism Isoleucine Kidney/cytology Molecular Sequence Data Phenylalanine Phosphorylation Recombinant Fusion Proteins/metabolism Serine/metabolism Subtilisins/genetics,metabolism
Chemicals
Amino Acids, Dicarboxylic Recombinant Fusion Proteins Isoleucine Serine Phenylalanine Subtilisins Furin
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Simmen T
Institute of Biochemistry, BIL Biomedical Research Center, University of Lausanne, CH-1066 Epalinges, Switzerland.
Nobile M
Bonifacino J S
Hunziker W
References (44)
44 references, click to expand
  1. Eukaryotic protein processing: endoproteolysis of precursor proteins.
    Curr Opin Biotechnol. 1997 Oct;8(5):602-7 PMID: 9353231
  2. Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin.
    EMBO J. 1995 Jun 1;14(11):2424-35 PMID: 7781597
  3. Predominant basolateral proteolytic processing of prosomatostatin into somatostatin-28 in polarized LLC-PK1 cells.
    Neuropeptides. 1997 Oct;31(5):393-8 PMID: 9413013
  4. Aggregation as a determinant of protein fate in post-Golgi compartments: role of the luminal domain of furin in lysosomal targeting.
    J Cell Biol. 1997 Dec 29;139(7):1735-45 PMID: 9412468
  5. A region from the medium chain adaptor subunit (mu) recognizes leucine- and tyrosine-based sorting signals.
    J Biol Chem. 1998 Apr 10;273(15):8638-45 PMID: 9535838
  6. Dileucine-based sorting signals bind to the beta chain of AP-1 at a site distinct and regulated differently from the tyrosine-based motif-binding site.
    EMBO J. 1998 Apr 15;17(8):2148-55 PMID: 9545228
  7. Furin: a mammalian subtilisin/Kex2p-like endoprotease involved in processing of a wide variety of precursor proteins.
    Biochem J. 1997 Nov 1;327 ( Pt 3):625-35 PMID: 9599222
  8. The leucine-based motif DDQxxLI is recognized both for internalization and basolateral sorting of invariant chain in MDCK cells.
    Eur J Cell Biol. 1998 May;76(1):25-32 PMID: 9650780
  9. PACS-1 defines a novel gene family of cytosolic sorting proteins required for trans-Golgi network localization.
    Cell. 1998 Jul 24;94(2):205-16 PMID: 9695949
  10. Regulation of endosome sorting by a specific PP2A isoform.
    J Cell Biol. 1998 Sep 21;142(6):1399-411 PMID: 9744873
  11. Biosynthetic transport of the asialoglycoprotein receptor H1 to the cell surface occurs via endosomes.
    Proc Natl Acad Sci U S A. 1995 Oct 24;92(22):10109-13 PMID: 7479735
  12. An acidic sequence within the cytoplasmic domain of furin functions as a determinant of trans-Golgi network localization and internalization from the cell surface.
    EMBO J. 1995 Oct 16;14(20):4961-75 PMID: 7588625
  13. 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. 1995 Nov 24;270(47):28397-401 PMID: 7499343
  14. Intracellular trafficking of furin is modulated by the phosphorylation state of a casein kinase II site in its cytoplasmic tail.
    EMBO J. 1995 Dec 1;14(23):5869-83 PMID: 8846780
  15. Different biosynthetic transport routes to the plasma membrane in BHK and CHO cells.
    J Cell Biol. 1996 Apr;133(2):247-56 PMID: 8609159
  16. A di-hydrophobic Leu-Val motif regulates the basolateral localization of CD44 in polarized Madin-Darby canine kidney epithelial cells.
    J Biol Chem. 1996 May 24;271(21):12185-90 PMID: 8647812
  17. Transport of vesicular stomatitis virus G protein to the cell surface is signal mediated in polarized and nonpolarized cells.
    J Cell Biol. 1996 May;133(3):543-58 PMID: 8636230
  18. Sorting of MHC class II molecules and the associated invariant chain (Ii) in polarized MDCK cells.
    J Cell Sci. 1997 Mar;110 ( Pt 5):597-609 PMID: 9092942
  19. Structural requirements for major histocompatibility complex class II invariant chain trafficking in polarized Madin-Darby canine kidney cells.
    J Biol Chem. 1997 May 2;272(18):11757-62 PMID: 9115230
  20. Clathrin-coated vesicle formation and protein sorting: an integrated process.
    Annu Rev Biochem. 1997;66:511-48 PMID: 9242916
  21. Linking cargo to vesicle formation: receptor tail interactions with coat proteins.
    Curr Opin Cell Biol. 1997 Aug;9(4):488-95 PMID: 9261055
  22. Interaction of furin in immature secretory granules from neuroendocrine cells with the AP-1 adaptor complex is modulated by casein kinase II phosphorylation.
    EMBO J. 1997 Aug 15;16(16):4859-70 PMID: 9305628
  23. Basolateral sorting of LDL receptor in MDCK cells: the cytoplasmic domain contains two tyrosine-dependent targeting determinants.
    Cell. 1992 Nov 27;71(5):741-53 PMID: 1423629
  24. Internalization and degradation of macrophage Fc receptors during receptor-mediated phagocytosis.
    J Cell Biol. 1983 Mar;96(3):887-95 PMID: 6833386
  25. Molecular cloning and expression of cDNAs for the human interleukin-2 receptor.
    Nature. 1984 Oct 18-24;311(5987):626-31 PMID: 6090948
  26. A monoclonal antibody 7G7/B6, binds to an epitope on the human interleukin-2 (IL-2) receptor that is distinct from that recognized by IL-2 or anti-Tac.
    Hybridoma. 1985 Summer;4(2):91-102 PMID: 2408992
  27. Expression of macrophage-lymphocyte Fc receptors in Madin-Darby canine kidney cells: polarity and transcytosis differ for isoforms with or without coated pit localization domains.
    J Cell Biol. 1989 Dec;109(6 Pt 2):3291-302 PMID: 2574723
  28. Identification, sequencing and expression of an integral membrane protein of the trans-Golgi network (TGN38).
    Biochem J. 1990 Aug 15;270(1):97-102 PMID: 2204342
  29. Structure and expression of mouse furin, a yeast Kex2-related protease. Lack of processing of coexpressed prorenin in GH4C1 cells.
    J Biol Chem. 1990 Dec 25;265(36):22075-8 PMID: 2266110
  30. Functional expression of furin demonstrating its intracellular localization and endoprotease activity for processing of proalbumin and complement pro-C3.
    J Biol Chem. 1991 Sep 5;266(25):16954-9 PMID: 1885622
  31. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant.
    Cell. 1991 Sep 6;66(5):907-20 PMID: 1909606
  32. Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen.
    J Biol Chem. 1992 Aug 15;267(23):16396-402 PMID: 1644824
  33. Anthrax toxin protective antigen is activated by a cell surface protease with the sequence specificity and catalytic properties of furin.
    Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10277-81 PMID: 1438214
  34. TGN38 is maintained in the trans-Golgi network by a tyrosine-containing motif in the cytoplasmic domain.
    EMBO J. 1993 May;12(5):2219-28 PMID: 8491209
  35. Expression of IL-2 receptors in human melanoma cells.
    Anticancer Res. 1993 May-Jun;13(3):555-64 PMID: 8317884
  36. Intracellular trafficking and activation of the furin proprotein convertase: localization to the TGN and recycling from the cell surface.
    EMBO J. 1994 Jan 1;13(1):18-33 PMID: 7508380
  37. An electron microscopic study of TGN38/41 dynamics.
    J Cell Sci Suppl. 1993;17:41-7 PMID: 8144704
  38. Retrieval of TGN proteins from the cell surface requires endosomal acidification.
    EMBO J. 1994 May 15;13(10):2305-12 PMID: 8194522
  39. A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells.
    EMBO J. 1994 Jul 1;13(13):2963-9 PMID: 8039492
  40. Structural requirements and sequence motifs for polarized sorting and endocytosis of LDL and Fc receptors in MDCK cells.
    J Cell Biol. 1994 Aug;126(4):991-1004 PMID: 8051216
  41. The cytoplasmic domain mediates localization of furin to the trans-Golgi network en route to the endosomal/lysosomal system.
    J Cell Biol. 1994 Sep;126(5):1157-72 PMID: 7914893
  42. Site-directed mutagenesis of double-stranded DNA by the polymerase chain reaction.
    Gene. 1994 Dec 30;151(1-2):119-23 PMID: 7828859
  43. Newly synthesized transferrin receptors can be detected in the endosome before they appear on the cell surface.
    J Biol Chem. 1995 May 5;270(18):10999-1003 PMID: 7738042
  44. Post-Golgi biosynthetic trafficking.
    J Cell Sci. 1997 Dec;110 ( Pt 24):3001-9 PMID: 9365270
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.19.4.3136
Published
1999-04-00
Pages
3136-44
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC84107
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.19.4.3136 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2