Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

Driessen, Christoph; Bryant, Rebecca A.R.; Lennon-Duménil, Ana-María; Villadangos, José A; Bryant, Paula Wolf; Shi, Guo‐Ping; Chapman, Harold A.; Ploegh, Hidde L.

doi:10.1083/jcb.147.4.775

Cited by 211 publications

(206 citation statements)

References 59 publications

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“…1c). At this stage, growth impairment, combined with a delay in fur development, enabled the identification of the cathepsin B Ϫ/Ϫ ͞L Ϫ/Ϫ (19,24). (c) Mortality diagram of wild-type (n ϭ 20, dashed line) and cathepsin B Ϫ/Ϫ ͞L Ϫ/Ϫ mice (n ϭ 14, solid line).…”

Section: Resultsmentioning

confidence: 99%

Neuronal loss and brain atrophy in mice lacking cathepsins B and L

Felbor

Kessler²,

Mothes³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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307

217

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Cathepsins B and L are widely expressed cysteine proteases implicated in both intracellular proteolysis and extracellular matrix remodeling. However, specific roles remain to be validated in vivo. Here we show that combined deficiency of cathepsins B and L in mice is lethal during the second to fourth week of life. Cathepsin B ؊/؊ ͞L ؊/؊ mice reveal a degree of brain atrophy not previously seen in mice. This is because of massive apoptosis of select neurons in the cerebral cortex and the cerebellar Purkinje and granule cell layers. Neurodegeneration is accompanied by pronounced reactive astrocytosis and is preceded by an accumulation of ultrastructurally and biochemically unique lysosomal bodies in large cortical neurons and by axonal enlargements. Our data demonstrate a pivotal role for cathepsins B and L in maintenance of the central nervous system.

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Section: Resultsmentioning

confidence: 99%

Neuronal loss and brain atrophy in mice lacking cathepsins B and L

Felbor

Kessler²,

Mothes³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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307

217

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“…Processing of Ii appears to be based on redundant protease activities (Costantino et al 2008) with the exception of the cleavage of the p10 intermediate degradation product into CLIP. This requires cathepsin S (Riese et al 1996;Driessen et al 1999;Nakagawa et al 1999;Shi et al 1999) or cathepsins L and F (Nakagawa et al 1998;Shi et al 2000), depending on the cell type. Degradation of the remaining transmembrane fragment requires the intramembrane endopeptidase SPPL2A (Beisner et al 2013;Bergmann et al 2013;Schneppenheim et al 2013).…”

Section: Biosynthesis Of Mhciimentioning

confidence: 99%

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Broeke

Wubbolts

Stoorvogel

2013

Cold Spring Harbor Perspectives in Biology

142

102

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For the initiation of adaptive immune responses, dendritic cells present antigenic peptides in association with major histocompatibility complex class II (MHCII) to naïve CD4 þ T lymphocytes. In this review, we discuss how antigen presentation is regulated through intracellular processing and trafficking of MHCII. Newly synthesized MHCII is chaperoned by the invariant chain to endosomes, where peptides from endocytosed pathogens can bind. In nonactivated dendritic cells, peptide-loaded MHCII is ubiquitinated and consequently sorted by the ESCRT machinery to intraluminal vesicles of multivesicular bodies, ultimately leading to lysosomal degradation. Ubiquitination of newly synthesized MHCII is blocked when dendritic cells are activated, now allowing its transfer to the cell surface. This mode of regulation for MHCII is a prime example of how molecular processing and sorting at multivesicular bodies can determine the expression of signaling receptors at the plasma membrane.

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“…Where indicated, reimmunoprecipitation for Ii was conducted after dissociation of the complex in PBS/1% SDS by boiling and subsequent dilution of the SDS. Ii was immunoprecipitated using the polyclonal Ab JV5 recognizing the N terminus of Ii (31).…”

Section: Pulse-chase and Immunoprecipitationmentioning

confidence: 99%

Asparagine Endopeptidase Is Not Essential for Class II MHC Antigen Presentation but Is Required for Processing of Cathepsin L in Mice

Maehr

Hang²,

Mintern³

et al. 2005

The Journal of Immunology

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104

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Class II MHC molecules survey the endocytic compartments of APCs and present antigenic peptides to CD4 T cells. In this context, lysosomal proteases are essential not only for the generation of antigenic peptides but also for proteolysis of the invariant chain to allow the maturation of class II MHC molecules. Recent studies with protease inhibitors have implicated the asparagine endopeptidase (AEP) in class II MHC-restricted Ag presentation. We now report that AEP-deficient mice show no differences in processing of the invariant chain or maturation of class II MHC products compared with wild-type mice. In the absence of AEP, presentation to primary T cells of OVA and myelin oligodendrocyte glycoprotein, two Ags that contain asparagine residues within or in proximity to the relevant epitopes was unimpaired. Cathepsin (Cat) L, a lysosomal cysteine protease essential for the development to CD4 and NK T cells, fails to be processed into its mature two-chain form in AEP-deficient cells. Despite this, the numbers of CD4 and NK T cells are normal, showing that the single-chain form of Cat L is sufficient for its function in vivo. We conclude that AEP is essential for processing of Cat L but not for class II MHC-restricted Ag presentation.

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Cathepsin S Controls the Trafficking and Maturation of Mhc Class II Molecules in Dendritic Cells

Cited by 211 publications

References 59 publications

Neuronal loss and brain atrophy in mice lacking cathepsins B and L

Neuronal loss and brain atrophy in mice lacking cathepsins B and L

MHC Class II Antigen Presentation by Dendritic Cells Regulated through Endosomal Sorting

Asparagine Endopeptidase Is Not Essential for Class II MHC Antigen Presentation but Is Required for Processing of Cathepsin L in Mice

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