The Chondroitin Sulfate Form of Invariant Chain Trimerizes with Conventional Invariant Chain and These Complexes Are Rapidly Transported from the Trans-Golgi Network to the Cell Surface

Overview

Journal Biochem J

Specialty Biochemistry

Date 2007 May 12

PMID 17492940

Citations 5

Authors

Lynne S Arneson

Jim Miller

Affiliations

Soon will be listed here.

Abstract

Targeting of MHCII-invariant chain complexes from the trans-Golgi network to endosomes is mediated by two di-leucine-based signals present in the cytosolic domain of invariant chain. Generation of this endosomal targeting signal is also dependent on multimerization of the invariant chain cytosolic domain sequences, mediated through assembly of invariant chain into homotrimers. A small subset of invariant chain is modified by the addition of chondroitin sulfate and is expressed on the cell surface in association with MHCII. In the present study, we have followed the biosynthetic pathway and route of intracellular transport of this proteoglycan form of invariant chain. We found that the efficiency of chondroitin sulfate modification can be increased by altering the invariant chain amino acid sequence around Ser-201 to the xylosylation consensus sequence. Our results also indicate that, following sulfation, the proteoglycan form is transported rapidly from the trans-Golgi network to the cell surface and is degraded following internalization into an endocytic compartment. Invariant chain-chondroitin sulfate is present in invariant chain trimers that also include conventional non-proteoglycan forms of invariant chain. These data indicate that invariant chain-chondroitin sulfate-containing complexes are transported rapidly from the trans-Golgi network to the cell surface in spite of the presence of an intact endosomal localization signal. Furthermore, these results suggest that invariant chain-chondroitin sulfate may play an important role in the generation of cell-surface pools of invariant chain that can serve as receptors for CD44 and macrophage migration inhibitory factor.

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References

Anderson M, Swier K, Arneson L, Miller J . Enhanced antigen presentation in the absence of the invariant chain endosomal localization signal. J Exp Med. 1993; 178(6):1959-69. PMC: 2191285. DOI: 10.1084/jem.178.6.1959. View

Roche P, Teletski C, Stang E, Bakke O, Long E . Cell surface HLA-DR-invariant chain complexes are targeted to endosomes by rapid internalization. Proc Natl Acad Sci U S A. 1993; 90(18):8581-5. PMC: 47401. DOI: 10.1073/pnas.90.18.8581. View

Bijlmakers M, Benaroch P, Ploegh H . Assembly of HLA DR1 molecules translated in vitro: binding of peptide in the endoplasmic reticulum precludes association with invariant chain. EMBO J. 1994; 13(11):2699-707. PMC: 395144. DOI: 10.1002/j.1460-2075.1994.tb06560.x. View

Zhang L, Esko J . Amino acid determinants that drive heparan sulfate assembly in a proteoglycan. J Biol Chem. 1994; 269(30):19295-9. View

Odorizzi C, Trowbridge I, Xue L, Hopkins C, DAVIS C, Collawn J . Sorting signals in the MHC class II invariant chain cytoplasmic tail and transmembrane region determine trafficking to an endocytic processing compartment. J Cell Biol. 1994; 126(2):317-30. PMC: 2200027. DOI: 10.1083/jcb.126.2.317. View

Bijlmakers M, Benaroch P, Ploegh H . Mapping functional regions in the lumenal domain of the class II-associated invariant chain. J Exp Med. 1994; 180(2):623-9. PMC: 2191624. DOI: 10.1084/jem.180.2.623. View

Benaroch P, Yilla M, Raposo G, Ito K, Miwa K, Geuze H . How MHC class II molecules reach the endocytic pathway. EMBO J. 1995; 14(1):37-49. PMC: 398050. DOI: 10.1002/j.1460-2075.1995.tb06973.x. View

Futter C, Connolly C, Cutler D, Hopkins C . Newly synthesized transferrin receptors can be detected in the endosome before they appear on the cell surface. J Biol Chem. 1995; 270(18):10999-1003. DOI: 10.1074/jbc.270.18.10999. View

Arneson L, Miller J . Efficient endosomal localization of major histocompatibility complex class II-invariant chain complexes requires multimerization of the invariant chain targeting sequence. J Cell Biol. 1995; 129(5):1217-28. PMC: 2120468. DOI: 10.1083/jcb.129.5.1217. View

10.

Warmerdam P, Long E, Roche P . Isoforms of the invariant chain regulate transport of MHC class II molecules to antigen processing compartments. J Cell Biol. 1996; 133(2):281-91. PMC: 2120797. DOI: 10.1083/jcb.133.2.281. View

11.

Shachar I, Flavell R . Requirement for invariant chain in B cell maturation and function. Science. 1996; 274(5284):106-8. DOI: 10.1126/science.274.5284.106. View

12.

Salamero J, Borgne R, Saudrais C, Goud B, Hoflack B . Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes. J Biol Chem. 1996; 271(48):30318-21. DOI: 10.1074/jbc.271.48.30318. View

13.

Brinkmann T, Weilke C, Kleesiek K . Recognition of acceptor proteins by UDP-D-xylose proteoglycan core protein beta-D-xylosyltransferase. J Biol Chem. 1997; 272(17):11171-5. DOI: 10.1074/jbc.272.17.11171. View

14.

Matza D, Wolstein O, Dikstein R, Shachar I . Invariant chain induces B cell maturation by activating a TAF(II)105-NF-kappaB-dependent transcription program. J Biol Chem. 2001; 276(29):27203-6. DOI: 10.1074/jbc.M104684200. View

15.

Rodionov D, Bakke O . Medium chains of adaptor complexes AP-1 and AP-2 recognize leucine-based sorting signals from the invariant chain. J Biol Chem. 1998; 273(11):6005-8. DOI: 10.1074/jbc.273.11.6005. View

16.

BOZZA M, Satoskar A, Lin G, Lu B, Humbles A, Gerard C . Targeted disruption of migration inhibitory factor gene reveals its critical role in sepsis. J Exp Med. 1999; 189(2):341-6. PMC: 2192995. DOI: 10.1084/jem.189.2.341. View

17.

Ashman J, Miller J . A role for the transmembrane domain in the trimerization of the MHC class II-associated invariant chain. J Immunol. 1999; 163(5):2704-12. View

18.

Dugast M, Toussaint H, Dousset C, Benaroch P . AP2 clathrin adaptor complex, but not AP1, controls the access of the major histocompatibility complex (MHC) class II to endosomes. J Biol Chem. 2005; 280(20):19656-64. DOI: 10.1074/jbc.M501357200. View

19.

McCormick P, Martina J, Bonifacino J . Involvement of clathrin and AP-2 in the trafficking of MHC class II molecules to antigen-processing compartments. Proc Natl Acad Sci U S A. 2005; 102(22):7910-5. PMC: 1138261. DOI: 10.1073/pnas.0502206102. View

20.

Becker-Herman S, Arie G, Medvedovsky H, Kerem A, Shachar I . CD74 is a member of the regulated intramembrane proteolysis-processed protein family. Mol Biol Cell. 2005; 16(11):5061-9. PMC: 1266406. DOI: 10.1091/mbc.e05-04-0327. View