Glycosylation signals that separate the trimerization from the MHC class II-binding domain control intracellular degradation of invariant chain

被引:18
作者
Neumann, J [1 ]
Schach, N [1 ]
Koch, N [1 ]
机构
[1] Univ Bonn, Immunobiol Sect, D-53117 Bonn, Germany
关键词
D O I
10.1074/jbc.M010629200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Invariant chain (Ii) serves as a chaperone for folding and intracellular transport of major histocompatibility complex class II (MHCII) molecules. Early in biosynthesis, Ii associates with MHCII molecules and directs their intracellular transport to endocytic compartments where vesicular proteinases sequentially release Ii from the MHCII heterodimer. The detachment of Ii makes the MHCII groove susceptible for binding of antigenic peptides. We investigated the role of N-linked glycosylation in the controlled intracellular degradation of Ii. Motifs for asparagine-linked glycosylation were altered, and mutated Ii (IiNmut) was transiently expressed in COS cells. The half-life of IiNmut was strongly reduced compared with wild-type Ii although the sensitivity of the N glycan-free polypeptide to in vitro proteinase digestion was not substantially increased. Inhibition of vesicular proteinases revealed endosomal degradation of IiNmut. Intracellular proteolysis of IiNmut is substantially impaired by serine proteinase inhibitors. Thus, a considerable amount of IiNmut is degraded in nonacidic intracellular compartments. The data suggest that N-linked glycosylation of Ii hinders premature proteolysis in nonacidic vesicles resulting in Ii degradation in acidic MHC class II-processing compartments.
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收藏
页码:13469 / 13475
页数:7
相关论文
共 45 条
[1]   INVARIANT CHAIN CLEAVAGE AND PEPTIDE LOADING IN MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-II VESICLES [J].
AMIGORENA, S ;
WEBSTER, P ;
DRAKE, J ;
NEWCOMB, J ;
CRESSWELL, P ;
MELLMAN, I .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 181 (05) :1729-1741
[2]   TRANSIENT ACCUMULATION OF NEW CLASS-II MHC MOLECULES IN A NOVEL ENDOCYTIC COMPARTMENT IN B-LYMPHOCYTES [J].
AMIGORENA, S ;
DRAKE, JR ;
WEBSTER, P ;
MELLMAN, I .
NATURE, 1994, 369 (6476) :113-120
[3]   INVARIANT CHAIN CAN FUNCTION AS A CHAPERONE PROTEIN FOR CLASS-II MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES [J].
ANDERSON, MS ;
MILLER, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (06) :2282-2286
[4]   EFFICIENT ENDOSOMAL LOCALIZATION OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS II-INVARIANT CHAIN COMPLEXES REQUIRES MULTIMERIZATION OF THE INVARIANT CHAIN TARGETING SEQUENCE [J].
ARNESON, LS ;
MILLER, J .
JOURNAL OF CELL BIOLOGY, 1995, 129 (05) :1217-1228
[5]   MHC CLASS-II-ASSOCIATED INVARIANT CHAIN CONTAINS A SORTING SIGNAL FOR ENDOSOMAL COMPARTMENTS [J].
BAKKE, O ;
DOBBERSTEIN, B .
CELL, 1990, 63 (04) :707-716
[6]   HOW MHC CLASS-II MOLECULES REACH THE ENDOCYTIC PATHWAY [J].
BENAROCH, P ;
YILLA, M ;
RAPOSO, G ;
ITO, K ;
MIWA, K ;
GEUZE, HJ ;
PLOEGH, HL .
EMBO JOURNAL, 1995, 14 (01) :37-49
[7]  
BERTOLINO P, 1995, J IMMUNOL, V154, P5620
[8]   MAPPING FUNCTIONAL REGIONS IN THE LUMENAL DOMAIN OF THE CLASS II-ASSOCIATED INVARIANT CHAIN [J].
BIJLMAKERS, MJE ;
BENAROCH, P ;
PLOEGH, HL .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 180 (02) :623-629
[9]   A region from the medium chain adaptor subunit (μ) recognizes leucine- and tyrosine-based sorting signals [J].
Bremnes, T ;
Lauvrak, V ;
Lindqvist, B ;
Bakke, O .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (15) :8638-8645
[10]  
BROSTERHUS H, 1994, POST TRANSLATIONAL M