Home LiteratureArticle Details
PMID: 16516837 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

A lumenal domain-dependent pathway for sorting to intralumenal vesicles of multivesicular endosomes involved in organelle morphogenesis.

Developmental cell ·Vol. 10 ·No. 3 ·2006-03-00 ·Pages 343-54

Theos AC, Truschel ST, Tenza D, Hurbain I, Harper DC, Berson JF, Thomas PC, Raposo G, Marks MS

Abstract

Cargo partitioning into intralumenal vesicles (ILVs) of multivesicular endosomes underlies such cellular processes as receptor downregulation, viral budding, and biogenesis of lysosome-related organelles such as melanosomes. We show that the melanosomal protein Pmel17 is sorted into ILVs by a mechanism that is dependent upon lumenal determinants and conserved in non-pigment cells. Pmel17 targeting to ILVs does not require its native cytoplasmic domain or cytoplasmic residues targeted by ubiquitylation and, unlike sorting of ubiquitylated cargo, is insensitive to functional inhibition of Hrs and ESCRT complexes. Chimeric protein and deletion analyses indicate that two N-terminal lumenal subdomains are necessary and sufficient for ILV targeting. Pmel17 fibril formation, which occurs during melanosome maturation in melanocytes, requires a third lumenal subdomain and proteolytic processing that itself requires ILV localization. These results establish an Hrs- and perhaps ESCRT-independent pathway of ILV sorting by lumenal determinants and a requirement for ILV sorting in fibril formation.

MeSH Terms
Antigens, Neoplasm Biomarkers/metabolism Cell Line Endosomes/metabolism Humans MART-1 Antigen Melanosomes/metabolism Membrane Glycoproteins/genetics,metabolism Morphogenesis Neoplasm Proteins/metabolism Organelles/metabolism Protein Transport Recombinant Fusion Proteins/genetics,metabolism Transport Vesicles/metabolism gp100 Melanoma Antigen
Chemicals
Antigens, Neoplasm Biomarkers MART-1 Antigen MLANA protein, human Membrane Glycoproteins Neoplasm Proteins PMEL protein, human Recombinant Fusion Proteins gp100 Melanoma Antigen
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Theos Alexander C
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Truschel Steven T
Tenza Daniele
Hurbain Ilse
Harper Dawn C
Berson Joanne F
Thomas Penelope C
Raposo Graça
Marks Michael S
References (60)
60 references, click to expand
  1. Spatial separation of HLA-DM/HLA-DR interactions within MIIC and phagosome-induced immune escape.
    Immunity. 2005 Feb;22(2):221-33 PMID: 15723810
  2. Role of mammalian vacuolar protein-sorting proteins in endocytic trafficking of a non-ubiquitinated G protein-coupled receptor to lysosomes.
    J Biol Chem. 2004 May 21;279(21):22522-31 PMID: 15024011
  3. Ubiquitylation of a melanosomal protein by HECT-E3 ligases serves as sorting signal for lysosomal degradation.
    Mol Biol Cell. 2005 Apr;16(4):1777-87 PMID: 15703212
  4. Ubiquitination on nonlysine residues by a viral E3 ubiquitin ligase.
    Science. 2005 Jul 1;309(5731):127-30 PMID: 15994556
  5. Depletion of TSG101 forms a mammalian "Class E" compartment: a multicisternal early endosome with multiple sorting defects.
    J Cell Sci. 2005 Jul 15;118(Pt 14):3003-17 PMID: 16014378
  6. The Silver locus product Pmel17/gp100/Silv/ME20: controversial in name and in function.
    Pigment Cell Res. 2005 Oct;18(5):322-36 PMID: 16162173
  7. Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes.
    Mol Biol Cell. 2005 Nov;16(11):5356-72 PMID: 16162817
  8. EGF stimulates annexin 1-dependent inward vesiculation in a multivesicular endosome subpopulation.
    EMBO J. 2006 Jan 11;25(1):1-12 PMID: 16052208
  9. Functional amyloid formation within mammalian tissue.
    PLoS Biol. 2006 Jan;4(1):e6 PMID: 16300414
  10. The endocytic pathway: a mosaic of domains.
    Nat Rev Mol Cell Biol. 2001 Oct;2(10):721-30 PMID: 11584299
  11. The melanosome: membrane dynamics in black and white.
    Nat Rev Mol Cell Biol. 2001 Oct;2(10):738-48 PMID: 11584301
  12. ATPase-defective mammalian VPS4 localizes to aberrant endosomes and impairs cholesterol trafficking.
    Mol Biol Cell. 2000 Jan;11(1):227-39 PMID: 10637304
  13. The mouse SKD1, a homologue of yeast Vps4p, is required for normal endosomal trafficking and morphology in mammalian cells.
    Mol Biol Cell. 2000 Feb;11(2):747-63 PMID: 10679028
  14. Pro-opiomelanocortin-related peptides, prohormone convertases 1 and 2 and the regulatory peptide 7B2 are present in melanosomes of human melanocytes.
    J Invest Dermatol. 2000 Mar;114(3):430-7 PMID: 10692100
  15. A common temperature-sensitive allelic form of human tyrosinase is retained in the endoplasmic reticulum at the nonpermissive temperature.
    J Biol Chem. 2000 Apr 21;275(16):12281-9 PMID: 10766867
  16. Lysosome-related organelles.
    FASEB J. 2000 Jul;14(10):1265-78 PMID: 10877819
  17. Involvement of the membrane lipid bilayer in sorting prohormone convertase 2 into the regulated secretory pathway.
    Biochem J. 2000 Aug 1;349 Pt 3:843-52 PMID: 10903147
  18. Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells.
    J Cell Biol. 2001 Feb 19;152(4):809-24 PMID: 11266471
  19. Ubiquitin-dependent sorting into the multivesicular body pathway requires the function of a conserved endosomal protein sorting complex, ESCRT-I.
    Cell. 2001 Jul 27;106(2):145-55 PMID: 11511343
  20. Sorting of proteins into multivesicular bodies: ubiquitin-dependent and -independent targeting.
    EMBO J. 2001 Sep 17;20(18):5176-86 PMID: 11566881
  21. Linking albinism and immunity: the secrets of secretory lysosomes.
    Science. 2004 Jul 2;305(5680):55-9 PMID: 15232098
  22. Exosomes: endosomal-derived vesicles shipping extracellular messages.
    Curr Opin Cell Biol. 2004 Aug;16(4):415-21 PMID: 15261674
  23. The human endosomal sorting complex required for transport (ESCRT-I) and its role in HIV-1 budding.
    J Biol Chem. 2004 Aug 20;279(34):36059-71 PMID: 15218037
  24. The small chemical vacuolin-1 inhibits Ca(2+)-dependent lysosomal exocytosis but not cell resealing.
    EMBO Rep. 2004 Sep;5(9):883-8 PMID: 15332114
  25. Retrovirus budding.
    Annu Rev Cell Dev Biol. 2004;20:395-425 PMID: 15473846
  26. A general method of in vitro preparation and specific mutagenesis of DNA fragments: study of protein and DNA interactions.
    Nucleic Acids Res. 1988 Aug 11;16(15):7351-67 PMID: 3045756
  27. Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences.
    J Biol Chem. 1988 Dec 15;263(35):18920-8 PMID: 3198605
  28. 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
  29. Oligomerized transferrin receptors are selectively retained by a lumenal sorting signal in a long-lived endocytic recycling compartment.
    J Cell Biol. 1995 Jun;129(6):1509-22 PMID: 7790351
  30. Aggregation reroutes molecules from a recycling to a vesicle-mediated secretion pathway during reticulocyte maturation.
    J Cell Sci. 1997 Aug;110 ( Pt 16):1867-77 PMID: 9296387
  31. 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
  32. The structure of a PKD domain from polycystin-1: implications for polycystic kidney disease.
    EMBO J. 1999 Jan 15;18(2):297-305 PMID: 9889186
  33. A protein's final ESCRT.
    Traffic. 2005 Jan;6(1):2-9 PMID: 15569240
  34. Saposin C-LBPA interaction in late-endosomes/lysosomes.
    Exp Cell Res. 2005 Feb 15;303(2):300-7 PMID: 15652344
  35. Pmel17 initiates premelanosome morphogenesis within multivesicular bodies.
    Mol Biol Cell. 2001 Nov;12(11):3451-64 PMID: 11694580
  36. Overexpression of the N-terminal domain of TSG101 inhibits HIV-1 budding by blocking late domain function.
    Proc Natl Acad Sci U S A. 2002 Jan 22;99(2):955-60 PMID: 11805336
  37. The dark side of lysosome-related organelles: specialization of the endocytic pathway for melanosome biogenesis.
    Traffic. 2002 Apr;3(4):237-48 PMID: 11929605
  38. Bilayered clathrin coats on endosomal vacuoles are involved in protein sorting toward lysosomes.
    Mol Biol Cell. 2002 Apr;13(4):1313-28 PMID: 11950941
  39. Hrs sorts ubiquitinated proteins into clathrin-coated microdomains of early endosomes.
    Nat Cell Biol. 2002 May;4(5):394-8 PMID: 11988743
  40. The Vps27p Hse1p complex binds ubiquitin and mediates endosomal protein sorting.
    Nat Cell Biol. 2002 Jul;4(7):534-9 PMID: 12055639
  41. The melanocytic protein Melan-A/MART-1 has a subcellular localization distinct from typical melanosomal proteins.
    Traffic. 2002 Sep;3(9):678-93 PMID: 12191019
  42. Receptor downregulation and multivesicular-body sorting.
    Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905 PMID: 12461556
  43. Intravacuolar membrane lysis in Saccharomyces cerevisiae. Does vacuolar targeting of Cvt17/Aut5p affect its function?
    J Biol Chem. 2003 Mar 7;278(10):7810-21 PMID: 12499386
  44. STAM and Hrs are subunits of a multivalent ubiquitin-binding complex on early endosomes.
    J Biol Chem. 2003 Apr 4;278(14):12513-21 PMID: 12551915
  45. Recycling compartments and the internal vesicles of multivesicular bodies harbor most of the cholesterol found in the endocytic pathway.
    Traffic. 2003 Apr;4(4):222-31 PMID: 12694561
  46. Proprotein convertase cleavage liberates a fibrillogenic fragment of a resident glycoprotein to initiate melanosome biogenesis.
    J Cell Biol. 2003 May 12;161(3):521-33 PMID: 12732614
  47. Defects in human immunodeficiency virus budding and endosomal sorting induced by TSG101 overexpression.
    J Virol. 2003 Jun;77(11):6507-19 PMID: 12743307
  48. Protein sorting into multivesicular endosomes.
    Curr Opin Cell Biol. 2003 Aug;15(4):446-55 PMID: 12892785
  49. Vps27 recruits ESCRT machinery to endosomes during MVB sorting.
    J Cell Biol. 2003 Aug 4;162(3):413-23 PMID: 12900393
  50. Hrs regulates multivesicular body formation via ESCRT recruitment to endosomes.
    J Cell Biol. 2003 Aug 4;162(3):435-42 PMID: 12900395
  51. The prohormone processing enzyme PC3 is a lipid raft-associated transmembrane protein.
    Biochemistry. 2003 Sep 9;42(35):10445-55 PMID: 12950171
  52. The UIM domain of Hrs couples receptor sorting to vesicle formation.
    J Cell Sci. 2003 Oct 15;116(Pt 20):4169-79 PMID: 12953068
  53. AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding.
    Cell. 2003 Sep 19;114(6):689-99 PMID: 14505569
  54. The protein network of HIV budding.
    Cell. 2003 Sep 19;114(6):701-13 PMID: 14505570
  55. Role of LBPA and Alix in multivesicular liposome formation and endosome organization.
    Science. 2004 Jan 23;303(5657):531-4 PMID: 14739459
  56. Endocytic recycling.
    Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32 PMID: 15040445
  57. The biogenesis of multivesicular endosomes.
    Nat Rev Mol Cell Biol. 2004 Apr;5(4):317-23 PMID: 15071556
  58. ATPase-deficient hVPS4 impairs formation of internal endosomal vesicles and stabilizes bilayered clathrin coats on endosomal vacuoles.
    J Cell Sci. 2004 Apr 1;117(Pt 9):1699-708 PMID: 15075231
  59. Degradation of AP2 during reticulocyte maturation enhances binding of hsc70 and Alix to a common site on TFR for sorting into exosomes.
    Traffic. 2004 Mar;5(3):181-93 PMID: 15086793
  60. Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein.
    Biochem Soc Trans. 2005 Apr;33(Pt 2):335-8 PMID: 15787600
Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1534-5807
DOI
10.1016/j.devcel.2006.01.012
Published
2006-03-00
Pages
343-54
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC1773005
Subset
IM
Grants
NCI NIH HHS · T32-CA-029141 · United States
NCI NIH HHS · T32 CA009140 · United States
NEI NIH HHS · R01 EY015625 · United States
NIAMS NIH HHS · R01 AR 041855 · United States
NIAMS NIH HHS · R01 AR048155 · United States
External Links
PubMed source DOI: 10.1016/j.devcel.2006.01.012 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