Your browser doesn't support javascript.
loading
: 20 | 50 | 100
1 - 2 de 2
1.
Cells ; 12(24)2023 12 08.
Article En | MEDLINE | ID: mdl-38132120

BACKGROUND: Proteins targeted by the ubiquitin proteasome system (UPS) are identified for degradation by the proteasome, which has been implicated in the development of neurodegenerative diseases. Major histocompatibility complex (MHC) molecules present peptides broken down by the proteasome and are involved in neuronal plasticity, regulating the synapse number and axon regeneration in the central or peripheral nervous system during development and in brain diseases. The mechanisms governing these effects are mostly unknown, but evidence from different compartments of the cerebral cortex indicates the presence of immune-like MHC receptors in the central nervous system. METHODS: We used human induced pluripotent stem cells (iPSCs) differentiated into neural stem cells and then into motor neurons as a developmental model to better understand the structure of the proteasome in developing motor neurons. We performed a proteomic analysis of starting human skin fibroblasts, their matching iPSCs, differentiated neural stem cells and motor neurons that highlighted significant differences in the constitutive proteasome and immunoproteasome subunits during development toward motor neurons from iPSCs. RESULTS: The proteomic analysis showed that the catalytic proteasome subunits expressed in fibroblasts differed from those in the neural stem cells and motor neurons. Western blot analysis confirmed the proteomic data, particularly the decreased expression of the ß5i (PSMB8) subunit immunoproteasome in MNs compared to HFFs and increased ß5 (PSMB5) in MNs compared to HFFs. CONCLUSION: The constitutive proteasome subunits are upregulated in iPSCs and NSCs from HFFs. Immunoproteasome subunit ß5i expression is higher in MNs than NSCs; however, overall, there is more of a constitutive proteasome structure in MNs when comparing HFFs to MNs. The proteasome composition may have implications for motor neuron development and neurodevelopmental diseases that warrant further investigation.


Induced Pluripotent Stem Cells , Neural Stem Cells , Humans , Induced Pluripotent Stem Cells/metabolism , Proteasome Endopeptidase Complex/metabolism , Axons/metabolism , Proteomics , Nerve Regeneration , Motor Neurons/metabolism , Neural Stem Cells/metabolism , Proteins/metabolism
2.
Cell Immunol ; 387: 104707, 2023 05.
Article En | MEDLINE | ID: mdl-36933326

MHC-I molecules of the HLA-B7 supertype preferentially bind peptides with proline at position 2. HLA-B*51:01 and B*51:08 present two predominant subpeptidomes, one with Pro2 and hydrophobic residues at P1, and another with Ala2 and Asp enriched at position 1. Here, we present a meta-analysis of the peptidomes presented by molecules of the B7 supertype to investigate the presence of subpeptidomes across different allotypes. Several allotypes presented subpeptidomes differing in the presence of Pro or another residue at P2. The Ala2 subpeptidomes preferred Asp1 except in HLA-B*54:01, where ligands with Ala2 contained Glu1. Sequence alignment and the analysis of crystal structures allowed us to propose positions 45 and 67 of the MHC heavy chain as relevant for the presence of subpeptidomes. Deciphering the principles behind the presence of subpeptidomes could improve our understanding of antigen presentation in other MHC-I molecules. Running title: HLA-B7 supertype subpeptidomes.


HLA-B7 Antigen , Histocompatibility Antigens Class I , Antigen Presentation , HLA-B Antigens/chemistry , HLA-B Antigens/metabolism , HLA-B7 Antigen/chemistry , HLA-B7 Antigen/metabolism , Peptides/metabolism , Humans
...