The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?

Bangert, Irina; Tumulka, Franz; Abele, Rupert

doi:10.1515/bc.2011.007

Cited by 15 publications

(13 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on our phylogenetic analysis, we found no homologs to TAP sequences (bootstrap value of 100 percent) in the insects, but insect homologs to the other human peptide transporters were identified. In accordance with the literature, we can also speculate that TAPL is the ancestor of the TAP family [95].…”

Section: Resultssupporting

confidence: 92%

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

et al. 2014

View full text Add to dashboard Cite

BackgroundInsects evolved ingenious adaptations to use extraordinary food sources. Particularly, the diet of herbivores enriched with noxious plant secondary metabolites requires detoxification mechanisms. Sequestration, which involves the uptake, transfer, and concentration of occasionally modified phytochemicals into specialized tissues or hemolymph, is one of the most successful detoxification strategies found in most insect orders. Due to the ability of ATP-binding cassette (ABC) carriers to transport a wide range of molecules including phytochemicals and xenobiotics, it is highly likely that they play a role in this sequestration process. To shed light on the role of ABC proteins in sequestration, we describe an inventory of putative ABC transporters in various tissues in the sequestering juvenile poplar leaf beetle, Chrysomela populi.ResultsIn the transcriptome of C. populi, we predicted 65 ABC transporters. To link the proteins with a possible function, we performed comparative phylogenetic analyses with ABC transporters of other insects and of humans. While tissue-specific profiling of each ABC transporter subfamily suggests that ABCB, C and G influence the plant metabolite absorption in the gut, ABCC with 14 members is the preferred subfamily responsible for the excretion of these metabolites via Malpighian tubules. Moreover, salicin, which is sequestered from poplar plants, is translocated into the defensive glands for further deterrent production. In these glands and among all identified ABC transporters, an exceptionally high transcript level was observed only for Cpabc35 (Cpmrp). RNAi revealed the deficiency of other ABC pumps to compensate the function of CpABC35, demonstrating its key role during sequestration.ConclusionWe provide the first comprehensive phylogenetic study of the ABC family in a phytophagous beetle species. RNA-seq data from different larval tissues propose the importance of ABC pumps to achieve a homeostasis of plant-derived compounds and offer a basis for future analyses of their physiological function in sequestration processes.

show abstract

Section: Resultssupporting

confidence: 92%

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

et al. 2014

View full text Add to dashboard Cite

show abstract

“…These data imply that class I molecules on the cell surface are internalized to an endolysosomal compartment where they intersect with peptides either supplied by the lysosomal polypeptide transporter ABCB9, also named TAP-like (TAPL) (for review, see Ref. 55) or those directly processed by lysosomal proteases. In addition, some of these HLA-B27-restricted peptides need further trimming by metallo-aminopeptidases sensitive to leucinethiol.…”

Section: Discussionmentioning

confidence: 99%

Allele-dependent Processing Pathways Generate the Endogenous Human Leukocyte Antigen (HLA) Class I Peptide Repertoire in Transporters Associated with Antigen Processing (TAP)-deficient Cells

Lorente

García

López

2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

The transporters associated with antigen processing (TAP) allow the supply of peptides derived from the cytosol to translocate to the endoplasmic reticulum, where they complex with nascent human leukocyte antigen (HLA) class I molecules. However, infected and tumor cells with TAP molecules blocked or individuals with nonfunctional TAP complexes are able to present HLA class I ligands generated by TAP-independent processing pathways. These peptides are detected by the CD8 ؉ lymphocyte cellular response. Here, the generation of the overall peptide repertoire associated with four different HLA class I molecules in TAP-deficient cells was studied. Using different protease inhibitors, four different proteolytic specificities were identified. These data demonstrate the different allele-dependent complex processing pathways involved in the generation of the HLA class I peptide repertoire in TAP-deficient cells.The newly synthesized proteome is sampled continuously by CD8 ϩ lymphocytes as short peptides presented by human leukocyte antigen (HLA) class I molecules at the cell surface. The majority of the peptides presented by HLA class I molecules are produced from proteolysis by the proteasome and other cytosolic proteases, such as tripeptidyl peptidase II (1-3), puromycin-sensitive aminopeptidase (4), insulin-degrading enzyme (5), thimet oligopeptidase (6), and caspases (7,8). These peptides are transported into the endoplasmic reticulum (ER) 2 by TAP, with subsequent N-terminal trimming by the metalloaminoproteases ERAP1 and 2 frequently being required (9, 10). Peptide binding to nascent HLA class I molecules generates stable peptide-HLA complexes that are exported to the cell membrane where are they exposed to cytotoxic CD8 ϩ T lymphocyte recognition (for review, see Ref. 11). TAP Ϫ/Ϫ humans (12) and mice (13) have a reduced functional CD8 ϩ population but do not appear to have an increased susceptibility to neoplasms or viral infections. Thus, the TAPindependent pathways may be sufficient to control these diseases and allow individuals with this HLA class I deficiency to live normal life spans with only a limited susceptibility to chronic respiratory bacterial infections. In addition, evidence for TAP-independent pathways of antigen presentation by MHC class I molecules of particular but diverse pathogenic epitopes was reported previously (for review, see Ref. 14 -16). The identified proteases involved in the generation of specific ligands in TAP-deficient cells include ER signal peptidase (SPase) (17, 18), ER signal peptide peptidase (SPPase) (19,20), trans-Golgi network furin (21, 22), and lysosomal cathepsins (23). However, systematic studies of TAP-independent pathways involved in the generation of the overall peptide repertoire associated with different HLA class I molecules have not been reported. Studying the reexpression of newly synthesized complexes of different HLA class I molecules in the presence of diverse protease inhibitors allowed the determination of several allele-dependent processing pathways in ...

show abstract

“…For BMDCs from Lamp-2-deficient mice, we also did not find a significant reduction of LC3-II conversion by Western blot analysis after infection, starvation, or chloroquine treatment in these cells, indicating no significant alterations of autophagy in Lamp-2 Ϫ/Ϫ BMDCs. Given that TAP and LAMP-2 were not involved in antigen presentation, other peptide transporters, like TAPL (transporter associated with antigen processing like) (52), might translocate the peptides into the endosomal/lysosomal compartment and seem to be reasonable candidates for further studies to address this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4 ⁺ T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

Thiele

Tao

Zhang

et al. 2015

J Virol

View full text Add to dashboard Cite

CD4؉ T lymphocytes play a central role in the immune system and mediate their function after recognition of their respective antigens presented on major histocompatibility complex II (MHCII) molecules on antigen-presenting cells (APCs). Conventionally, phagocytosed antigens are loaded on MHCII for stimulation of CD4 ؉ T cells. Certain epitopes, however, can be processed directly from intracellular antigens and are presented on MHCII (endogenous MHCII presentation). Here we characterized the MHCII antigen presentation pathways that are possibly involved in the immune response upon vaccination with modified vaccinia virus Ankara (MVA), a promising live viral vaccine vector. We established CD4؉ T-cell lines specific for MVA-derived epitopes as tools for in vitro analysis of MHCII antigen processing and presentation in MVA-infected APCs. We provide evidence that infected APCs are able to directly transfer endogenous viral proteins into the MHCII pathway to efficiently activate CD4 ؉ T cells. By using knockout mice and chemical inhibitory compounds, we further elucidated the molecular basis, showing that among the various subcellular pathways investigated, proteasomes and autophagy are key players in the endogenous MHCII presentation during MVA infection. Interestingly, although proteasomal processing plays an important role, neither TAP nor LAMP-2 was found to be involved in the peptide transport. Defining the molecular mechanism of MHCII presentation during MVA infection provides a basis for improving MVA-based vaccination strategies by aiming for enhanced CD4 ؉ T-cell activation by directing antigens into the responsible pathways. IMPORTANCEThis work contributes significantly to our understanding of the immunogenic properties of pathogens by deciphering antigen processing pathways contributing to efficient activation of antigen-specific CD4 ؉ T cells. We identified autophagosome formation, proteasomal activity, and lysosomal integrity as being crucial for endogenous CD4 ؉ T-cell activation. Since poxvirus vectors such as MVA are already used in clinical trials as recombinant vaccines, the data provide important information for the future design of optimized poxviral vaccines for the study of advanced immunotherapy options.

show abstract

The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?

Cited by 15 publications

References 37 publications

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

Allele-dependent Processing Pathways Generate the Endogenous Human Leukocyte Antigen (HLA) Class I Peptide Repertoire in Transporters Associated with Antigen Processing (TAP)-deficient Cells

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4 ⁺ T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

Contact Info

Product

Resources

About

The lysosomal polypeptide transporter TAPL: more than a housekeeping factor?

Cited by 15 publications

References 37 publications

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

Tissue-Specific Transcript Profiling for ABC Transporters in the Sequestering Larvae of the Phytophagous Leaf Beetle Chrysomela populi

Allele-dependent Processing Pathways Generate the Endogenous Human Leukocyte Antigen (HLA) Class I Peptide Repertoire in Transporters Associated with Antigen Processing (TAP)-deficient Cells

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4 + T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways

Contact Info

Product

Resources

About

Modified Vaccinia Virus Ankara-Infected Dendritic Cells Present CD4 ⁺ T-Cell Epitopes by Endogenous Major Histocompatibility Complex Class II Presentation Pathways