Home LiteratureArticle Details
PMID: 8039492 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A di-leucine motif mediates endocytosis and basolateral sorting of macrophage IgG Fc receptors in MDCK cells.

The EMBO journal ·Vol. 13 ·No. 13 ·1994-07-01 ·Pages 2963-9

Hunziker W, Fumey C

Abstract

An important function of the low affinity IgG Fc receptor FcRII-B2 (FcR) on macrophages is the internalization of soluble antigen-antibody complexes for lysosomal degradation. Most endocytic receptors possess tyrosine-containing cytoplasmic determinants required for endocytosis. In many proteins, signals which overlap with the endocytosis determinant and share the same critical tyrosine residue also mediate basolateral sorting in the trans-Golgi network of epithelial cells. Despite the presence of two tyrosine residues in the FcR cytosolic domain, neither one is absolutely required for coated pit localization or basolateral targeting. Nevertheless, a short domain of 13 residues containing one of the non-critical tyrosine residues mediates endocytosis and basolateral delivery. Alanine scan mutagenesis of this region now revealed a critical role of a leucine-leucine motif in both events. These findings suggest that endocytosis and basolateral sorting can be mediated by both tyrosine- and di-leucine-based signals and confirm the close relationship between the two determinants already observed for 'classical' tyrosine-dependent motifs.

MeSH Terms
Amino Acid Sequence Antigen-Antibody Complex/metabolism Biological Transport/physiology Cell Line Cell Membrane/metabolism Cell Polarity/physiology Cytoplasm/metabolism Endocytosis/physiology Golgi Apparatus/metabolism Immunoglobulin Fab Fragments/metabolism Immunoglobulin G/metabolism Kinetics Leucine/physiology Macrophages/cytology,physiology Molecular Sequence Data Mutagenesis, Site-Directed Receptors, IgG/genetics,physiology
Chemicals
Antigen-Antibody Complex Immunoglobulin Fab Fragments Immunoglobulin G Receptors, IgG Leucine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Hunziker W
Institute of Biochemistry, University of Lausanne, Epalinges, Switzerland.
Fumey C
References (62)
62 references, click to expand
  1. A single amino acid change in the cytoplasmic domain allows the influenza virus hemagglutinin to be endocytosed through coated pits.
    Cell. 1988 Jun 3;53(5):743-52 PMID: 2897244
  2. Structure and expression of human IgG FcRII(CD32). Functional heterogeneity is encoded by the alternatively spliced products of multiple genes.
    J Exp Med. 1989 Oct 1;170(4):1369-85 PMID: 2529342
  3. An Fc receptor structurally related to MHC class I antigens.
    Nature. 1989 Jan 12;337(6203):184-7 PMID: 2911353
  4. Transmembrane signals and intracellular "second messengers" in the regulation of quiescent B-lymphocyte activation.
    Immunol Rev. 1987 Feb;95:37-57 PMID: 2437013
  5. Accumulation of membrane glycoproteins in lysosomes requires a tyrosine residue at a particular position in the cytoplasmic tail.
    J Cell Biol. 1990 Sep;111(3):955-66 PMID: 2391371
  6. Localization of the signal for rapid internalization of the bovine cation-independent mannose 6-phosphate/insulin-like growth factor-II receptor to amino acids 24-29 of the cytoplasmic tail.
    J Biol Chem. 1991 Mar 25;266(9):5682-8 PMID: 1848556
  7. A His-Leu-Leu sequence near the carboxyl terminus of the cytoplasmic domain of the cation-dependent mannose 6-phosphate receptor is necessary for the lysosomal enzyme sorting function.
    J Biol Chem. 1992 Aug 25;267(24):17110-5 PMID: 1324923
  8. The essential tyrosine of the internalization signal in lysosomal acid phosphatase is part of a beta turn.
    Cell. 1991 Dec 20;67(6):1203-9 PMID: 1760845
  9. Mutational and secondary structural analysis of the basolateral sorting signal of the polymeric immunoglobulin receptor.
    J Cell Biol. 1993 Dec;123(5):1149-60 PMID: 8245123
  10. Internalization and degradation of macrophage Fc receptors bound to polyvalent immune complexes.
    J Cell Biol. 1984 Apr;98(4):1170-7 PMID: 6715404
  11. 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
  12. The structure of an endocytosis signal.
    Trends Cell Biol. 1992 Jul;2(7):189-92 PMID: 14731499
  13. Plasma membrane protein sorting in polarized epithelial cells.
    J Cell Biol. 1992 Feb;116(3):577-83 PMID: 1730769
  14. In vitro binding of the asialoglycoprotein receptor to the beta adaptin of plasma membrane coated vesicles.
    EMBO J. 1991 Dec;10(12):3735-42 PMID: 1935897
  15. Organization of the human and mouse low-affinity Fc gamma R genes: duplication and recombination.
    Science. 1990 May 11;248(4956):732-5 PMID: 2139735
  16. Basolateral sorting in MDCK cells requires a distinct cytoplasmic domain determinant.
    Cell. 1991 Sep 6;66(5):907-20 PMID: 1909606
  17. Endocytosis of the transferrin receptor requires the cytoplasmic domain but not its phosphorylation site.
    Cell. 1987 May 8;49(3):423-31 PMID: 3568132
  18. Differential microtubule requirements for transcytosis in MDCK cells.
    EMBO J. 1990 Nov;9(11):3515-25 PMID: 2170116
  19. Internalization and rapid recycling of macrophage Fc receptors tagged with monovalent antireceptor antibody: possible role of a prelysosomal compartment.
    J Cell Biol. 1984 Apr;98(4):1163-9 PMID: 6715403
  20. Transport of macrophage Fc receptors and Fc receptor-bound ligands to lysosomes.
    J Exp Med. 1986 Apr 1;163(4):952-71 PMID: 3950548
  21. Structural Aspects and Heterogeneity of Immunoglobulin Fc Receptors.
    Adv Immunol. 1981;31:247-70 PMID: 7032255
  22. A single amino acid change in the cytoplasmic domain alters the polarized delivery of influenza virus hemagglutinin.
    J Cell Biol. 1991 Aug;114(3):413-21 PMID: 1860878
  23. Endocytosis of antigen, anti-idiotype, and anti-immunoglobulin antibodies and receptor re-expression by murine B cells.
    J Immunol. 1989 Sep 15;143(6):1768-76 PMID: 2789248
  24. Cytoplasmic sequence required for basolateral targeting of LDL receptor in livers of transgenic mice.
    J Cell Biol. 1992 Apr;117(1):39-46 PMID: 1556156
  25. 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
  26. The murine Fc receptor for immunoglobulin: purification, partial amino acid sequence, and isolation of cDNA clones.
    Proc Natl Acad Sci U S A. 1986 Sep;83(18):6980-4 PMID: 2944118
  27. Receptor signalling and crosstalk in B lymphocytes.
    Immunol Rev. 1987 Oct;99:19-38 PMID: 2824341
  28. Internalization and degradation of macrophage Fc receptors during receptor-mediated phagocytosis.
    J Cell Biol. 1983 Mar;96(3):887-95 PMID: 6833386
  29. The internalization signal and the phosphorylation site of transferrin receptor are distinct from the main basolateral sorting information.
    EMBO J. 1993 Apr;12(4):1713-21 PMID: 8467813
  30. Polarity signals.
    Cell. 1991 Sep 6;66(5):827-9 PMID: 1653646
  31. Transferrin receptor internalization sequence YXRF implicates a tight turn as the structural recognition motif for endocytosis.
    Cell. 1990 Nov 30;63(5):1061-72 PMID: 2257624
  32. The cytoplasmic domain of the polymeric immunoglobulin receptor contains two internalization signals that are distinct from its basolateral sorting signal.
    J Biol Chem. 1992 May 15;267(14):9925-32 PMID: 1577823
  33. Cross-linking of B lymphocyte Fc gamma receptors and membrane immunoglobulin inhibits anti-immunoglobulin-induced blastogenesis.
    J Immunol. 1984 Feb;132(2):627-32 PMID: 6228594
  34. Fc receptor isoforms exhibit distinct abilities for coated pit localization as a result of cytoplasmic domain heterogeneity.
    Cell. 1989 Jul 28;58(2):317-27 PMID: 2568890
  35. Structural heterogeneity and functional domains of murine immunoglobulin G Fc receptors.
    Science. 1986 Nov 7;234(4777):718-25 PMID: 2946078
  36. A complementary DNA clone for a macrophage-lymphocyte Fc receptor.
    Nature. 1986 Nov 27-Dec 3;324(6095):372-5 PMID: 3024012
  37. Related signals for endocytosis and basolateral sorting of the asialoglycoprotein receptor.
    J Biol Chem. 1993 Oct 5;268(28):20772-7 PMID: 8407903
  38. The internalization signal in the cytoplasmic tail of lysosomal acid phosphatase consists of the hexapeptide PGYRHV.
    EMBO J. 1992 Dec;11(12):4391-9 PMID: 1425575
  39. In vitro binding of plasma membrane-coated vesicle adaptors to the cytoplasmic domain of lysosomal acid phosphatase.
    J Biol Chem. 1993 Jun 15;268(17):12537-43 PMID: 8509395
  40. Human IgG Fc receptor (hFcRII; CD32) exists as multiple isoforms in macrophages, lymphocytes and IgG-transporting placental epithelium.
    EMBO J. 1989 Dec 1;8(12):3657-66 PMID: 2531080
  41. NPXY, a sequence often found in cytoplasmic tails, is required for coated pit-mediated internalization of the low density lipoprotein receptor.
    J Biol Chem. 1990 Feb 25;265(6):3116-23 PMID: 1968060
  42. Mutational analysis of the cytoplasmic tail of the human transferrin receptor. Identification of a sub-domain that is required for rapid endocytosis.
    J Biol Chem. 1991 Oct 5;266(28):19006-12 PMID: 1918016
  43. Molecular sorting in polarized and non-polarized cells: common problems, common solutions.
    J Cell Sci Suppl. 1993;17:1-7 PMID: 8144683
  44. Role of the human transferrin receptor cytoplasmic domain in endocytosis: localization of a specific signal sequence for internalization.
    J Cell Biol. 1990 Feb;110(2):283-94 PMID: 2298808
  45. Cytoplasmic domain heterogeneity and functions of IgG Fc receptors in B lymphocytes.
    Science. 1992 Jun 26;256(5065):1808-12 PMID: 1535455
  46. An autonomous signal for basolateral sorting in the cytoplasmic domain of the polymeric immunoglobulin receptor.
    Cell. 1991 Jul 12;66(1):65-75 PMID: 2070419
  47. The NPXY internalization signal of the LDL receptor adopts a reverse-turn conformation.
    Cell. 1991 Dec 20;67(6):1195-201 PMID: 1760844
  48. Characterization of a monoclonal antibody directed against mouse macrophage and lymphocyte Fc receptors.
    J Exp Med. 1979 Sep 19;150(3):580-96 PMID: 90108
  49. The cytoplasmic tail of lysosomal acid phosphatase contains overlapping but distinct signals for basolateral sorting and rapid internalization in polarized MDCK cells.
    EMBO J. 1993 May;12(5):2181-93 PMID: 8491206
  50. Mutations in the cytoplasmic domain of the 275 kd mannose 6-phosphate receptor differentially alter lysosomal enzyme sorting and endocytosis.
    Cell. 1989 Jun 2;57(5):787-96 PMID: 2541923
  51. Human transferrin receptor internalization is partially dependent upon an aromatic amino acid on the cytoplasmic domain.
    Cell Regul. 1990 Mar;1(4):369-77 PMID: 2100204
  52. Specificity of binding of clathrin adaptors to signals on the mannose-6-phosphate/insulin-like growth factor II receptor.
    EMBO J. 1989 Apr;8(4):1041-7 PMID: 2545438
  53. Isolation of cDNAs for two distinct human Fc receptors by ligand affinity cloning.
    EMBO J. 1988 Apr;7(4):1053-9 PMID: 3402431
  54. Vesicular stomatitis virus glycoprotein contains a dominant cytoplasmic basolateral sorting signal critically dependent upon a tyrosine.
    J Biol Chem. 1993 Feb 15;268(5):3313-20 PMID: 8381425
  55. Relationships between sorting in the exocytic and endocytic pathways of MDCK cells.
    Semin Cell Biol. 1991 Dec;2(6):397-410 PMID: 1813029
  56. A novel di-leucine motif and a tyrosine-based motif independently mediate lysosomal targeting and endocytosis of CD3 chains.
    Cell. 1992 Jun 26;69(7):1143-57 PMID: 1535555
  57. Role of oxygen-dependent mechanisms in antibody-induced lysis of tumor cells by activated macrophages.
    J Exp Med. 1980 Jul 1;152(1):198-208 PMID: 6995553
  58. Isolation and expression of cDNA clones encoding a human receptor for IgG (Fc gamma RII).
    J Exp Med. 1987 Dec 1;166(6):1668-84 PMID: 2824655
  59. The low density lipoprotein receptor. Identification of amino acids in cytoplasmic domain required for rapid endocytosis.
    J Biol Chem. 1987 Mar 25;262(9):4075-82 PMID: 3104336
  60. Transport of the lysosomal membrane glycoprotein lgp120 (lgp-A) to lysosomes does not require appearance on the plasma membrane.
    J Cell Biol. 1992 Apr;117(2):311-25 PMID: 1560028
  61. Fc receptor endocytosis is controlled by a cytoplasmic domain determinant that actively prevents coated pit localization.
    J Cell Biol. 1992 Feb;116(4):875-88 PMID: 1734021
  62. An internal deletion in the cytoplasmic tail reverses the apical localization of human NGF receptor in transfected MDCK cells.
    J Cell Biol. 1991 Nov;115(3):607-18 PMID: 1655809
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1994-07-01
Pages
2963-9
Language
English
Region
England
NLM ID
8208664
PMCID
PMC395183
Subset
IM
External Links
PubMed source 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