Lamp-2a Facilitates MHC Class II Presentation of Cytoplasmic Antigens

Zhou, Dao‐Xiu; Li, Ping; Lin, Yinling; Lott, Jeremy M.; Hislop, Andrew D.; Canaday, David H.; Brutkiewicz, Randy R.; Blum, Janice S.

doi:10.1016/j.immuni.2005.03.009

Cited by 268 publications

(272 citation statements)

References 43 publications

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“…The CMA machinery, including heat shock cognate protein of 70 kDa (hsc70) that selects peptide substrates, and multimeric lysosomal-associated membrane protein 2A (LAMP-2A) complex, facilitates the entry of peptide into the lysosome (Orenstein and Cuervo, 2010;Li et al, 2011b). MHCII antigen presentation of cytosolic glutamate decarboxylase in human B lymphoblastoid cells is reduced following knockdown of LAMP-2 or hsc70 (Zhou et al, 2005). In addition, overexpression of LAMP-2A or hsc70 increases MHCII presentation of cytosolic glutamate decarboxylate.…”

Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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Traditionally, macroautophagy (autophagy) is viewed as a pathway of cell survival. Autophagy ensures the elimination of damaged or unwanted cytosolic components and provides a source of cellular nutrients during periods of stress. Interestingly, autophagy can also directly intersect with, and impact, other major pathways of cellular function. Here, we will review the contribution of autophagy to pathways of antigen presentation. The autophagy machinery acts to modulate both MHCI and MHCII antigen presentation. As such autophagy is an important participant in pathways that elicit host cell immunity and the elimination of infectious pathogens.

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Section: Autophagy In Mhc Class II Antigen Presentationmentioning

confidence: 99%

Intersection of autophagy with pathways of antigen presentation

Patterson

Mintern

2012

Protein Cell

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Section: Molecular Mechanisms Of Cmamentioning

confidence: 99%

“…However, recent studies have revealed that CMA is involved in antigen processing and presentation. The levels of autoantigen presentation are closely related to CMA activity [45][46][47] .As the two major proteolytic systems mediating the degradation of intracellular proteins [48,49] , the ALP and the UPS are not isolated and independent but tightly coordinated. CMA may affect the UPS and the other two autophagic pathways, and the UPS and the other two autophagic pathways can also modulate CMA activity.…”

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confidence: 99%

Chaperone-mediated autophagy: roles in neuroprotection

et al. 2015

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Chaperone-mediated autophagy (CMA), one of the main pathways of lysosomal proteolysis, is characterized by the selective targeting and direct translocation into the lysosomal lumen of substrate proteins containing a targeting motif biochemically related to the pentapeptide KFERQ. Along with the other two lysosomal pathways, macro-and micro-autophagy, CMA is essential for maintaining cellular homeostasis and survival by selectively degrading misfolded, oxidized, or damaged cytosolic proteins. CMA plays an important role in pathologies such as cancer, kidney disorders, and neurodegenerative diseases. Neurons are post-mitotic and highly susceptible to dysfunction of cellular quality-control systems. Maintaining a balance between protein synthesis and degradation is critical for neuronal functions and homeostasis. Recent studies have revealed several new mechanisms by which CMA protects neurons through regulating factors critical for their viability and homeostasis. In the current review, we summarize recent advances in the understanding of the regulation and physiology of CMA with a specifi c focus on its possible roles in neuroprotection.Keywords: chaperone-mediated autophagy; cellular homeostasis; neuroprotection; neuronal death; neurodegenerative disease ·Review· IntroductionMaintaining the balance between protein synthesis and degradation contributes to cellular homeostasis [1][2][3] . The ubiquitin-proteasome system (UPS) and the autophagylysosome pathway (ALP) are major systems present in almost all cell types to mediate the degradation of intracellular proteins into their constitutive amino-acids [4,5] .The UPS is a multi-subunit protease complex that degrades proteins tagged with one or more covalently-bound ubiquitin molecules, and most proteasome substrates are proteins with a short half-life [6,7] .In contrast to the UPS, the ALP is mainly responsible for the degradation of long-lived proteins and organelles.On the basis of the mechanism used for delivery of intracellular cargoes to lysosomes, autophagy can be divided into three types: macroautophagy (MA), microautophagy, and chaperone-mediated autophagy (CMA) [8,9] . Both CMA and MA have been identified in mammals as processes important for damage and diseases of the central nervous system [10] . MA is a bulk degradation system that involves the formation of a double-membrane structure (autophagosome) that sequesters damaged organelles and proteins. The autophagosome acquires the hydrolytic enzymes necessary to degrade its cargo by fusing with lysosomes [11] . Microautophagy traps nonspecifi c cytoplasm inside vesicles via direct invagination of the lysosomal membrane. These vesicles "pinch off" into the lumen and are degraded by lysosomal hydrolases [12] .CMA is the third type of autophagy, and has so far been found only in mammalian cells [13,14] . One of its intrinsic features is the selective targeting and direct translocation into the lysosomal lumen of substrate proteins containing a targeting motif related to the pentapeptide KFERQ [15,16] [17][1...

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“…33,40 For this pathway, peptides seem to be imported directly into endosomal/lysosomal compartments, via a transporter that was recently suggested to be Lamp-2a, the transporter of chaperone-mediated autophagy. 47 In addition to these proteasome-dependent pathways, cytosolic and nuclear proteins can also be processed by a proteasome-and TAPindependent pathway: This fourth pathway involves the direct import of cytosolic/nuclear proteins (e.g. the EBV nuclear antigen 1 (EBNA1) 30,31 ) into endosomes/lysosomes and is in part mediated by autophagy.…”

Section: Endogenous Mhc Class II Processingmentioning

confidence: 99%

“…It is thought that peptides are directly imported into endosomal/lysosomal compartments via a peptide transporter, possibly Lamp-2a. 47 (4) Cytosolic and nuclear proteins (e.g. the EBV nuclear antigen 1 (EBNA1) 31 ) can be processed by lysosomal proteases after direct import into endosomal/lysosomal compartments failed to be detected by M1-specific CD4 þ T cells, but stimulated M1-specific CD8 þ T cells.…”

Section: Proteasome-and Tap-independent Processing Of Cytosolic and Nmentioning

confidence: 99%

Immune surveillance of intracellular pathogens via autophagy

Schmid

Münz

2005

Cell Death Differ

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MHC class II molecules are thought to present peptides derived from extracellular proteins to CD4 þ T cells, which are important mediators of adaptive immunity to infections. In contrast, autophagy delivers constitutively cytosolic material for lysosomal degradation and has so far been recognized as an efficient mechanism of innate immunity against bacteria and viruses. Recent studies, however, link these two pathways and suggest that intracellular cytosolic and nuclear antigens are processed for MHC class II presentation after autophagy.

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Lamp-2a Facilitates MHC Class II Presentation of Cytoplasmic Antigens

Cited by 268 publications

References 43 publications

Intersection of autophagy with pathways of antigen presentation

Intersection of autophagy with pathways of antigen presentation

Chaperone-mediated autophagy: roles in neuroprotection

Immune surveillance of intracellular pathogens via autophagy

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