ESCRT-III on endosomes: new functions, new activation pathway

2016 ◽  
Vol 473 (2) ◽  
pp. e5-e8 ◽  
Author(s):  
Philip Woodman
Keyword(s):  
Mhc Class I ◽  
Protein Tyrosine Phosphatase ◽  
Protein Complexes ◽  
Tyrosine Phosphatase ◽  
Multivesicular Body ◽  
Class I ◽  
Recent Issue ◽  
Endosomal Sorting ◽  
Histocompatibility Complex ◽  
Biochemical Journal

The multivesicular body (MVB) pathway sorts ubiquitinated membrane cargo to intraluminal vesicles (ILVs) within the endosome, en route to the lysosomal lumen. The pathway involves the sequential action of conserved protein complexes [endosomal sorting complexes required for transport (ESCRTs)], culminating in the activation by ESCRT-II of ESCRT-III, a membrane-sculpting complex. Although this linear pathway of ESCRT activation is widely accepted, a study by Luzio and colleagues in a recent issue of the Biochemical Journal suggests that there is greater complexity in ESCRT-III activation, at least for some MVB cargoes. They show that ubiquitin-dependent sorting of major histocompatibility complex (MHC) class I to the MVB requires the central ESCRT-III complex but does not involve either ESCRT-II or functional links between ESCRT-II and ESCRT-III. Instead, they propose that MHC class I utilizes histidine-domain protein tyrosine phosphatase (HD-PTP), a non-canonical ESCRT interactor, to promote ESCRT-III activation.

scholarly journals His Domain Protein Tyrosine Phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation

2021 ◽  
Author(s):  
Gabrielle Parkinson ◽  
Peristera Roboti ◽  
Ling Zhang ◽  
Sandra Taylor ◽  
Philip Woodman
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Tyrosine Phosphatase ◽  
Multivesicular Body ◽  
Nucleotide Exchange ◽  
Protein Tyrosine ◽  
Endosomal Sorting ◽  
Binding Domains ◽  
Nucleotide Exchange Factor ◽  
Lysosomal Sorting ◽  
Domain Protein

His Domain Protein Tyrosine Phosphatase (HD-PTP) collaborates with Endosomal Sorting Complexes Required for Transport (ESCRTs) to sort endosomal cargo into intralumenal vesicles, forming the multivesicular body. Completion of multivesicular body sorting is accompanied by maturation of the endosome into a late endosome, an event that requires inactivation of the early endosomal GTPase, Rab5. Here we show that HD-PTP links ESCRT function with endosomal maturation. HD-PTP depletion prevents multivesicular body sorting, whilst also blocking cargo from exiting Rab5-rich endosomes. HD-PTP depleted cells contain hyperphosphorylated Rabaptin-5, a cofactor for the Rab5 guanine nucleotide exchange factor, Rabex-5, though HD-PTP is unlikely to directly dephosphorylate Rabaptin-5. In addition, HD-PTP depleted cells exhibit Rabaptin-5 dependent hyperactivation of Rab5. HD-PTP binds directly to Rabaptin-5, between its Rabex-5 and Rab5 binding domains. This binding reaction involves the ESCRT-0/ESCRT-III binding site in HD-PTP and is competed by an ESCRT-III peptide. Jointly, these findings indicate that HD-PTP may alternately scaffold ESCRTs and modulate Rabex-5/Rabaptin-5 activity, thereby helping to coordinate the completion of MVB sorting with endosomal maturation.

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

2015 ◽  
Vol 167 (3-4) ◽  
pp. 166-170
Author(s):  
Larissa Sarmento dos Santos ◽  
Juliana Pinto da Silva Mol ◽  
Auricélio Alves de Macedo ◽  
Ana Patrícia Carvalho Silva ◽  
Diego Luiz dos Santos Ribeiro ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Brucella Abortus ◽  
Class I ◽  
Major Histocompatibility ◽  
Bovine Placenta ◽  
Histocompatibility Complex

scholarly journals Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

1997 ◽  
Vol 8 (1) ◽  
pp. 47-57 ◽  
Author(s):  
E Stang ◽  
J Kartenbeck ◽  
R G Parton
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mammalian Cells ◽  
Simian Virus 40 ◽  
Class I ◽  
Major Histocompatibility ◽  
Surface Binding ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

Nonimmune thyroid destruction results from transgenic overexpression of an allogeneic major histocompatibility complex class I protein

1993 ◽  
Vol 13 (3) ◽  
pp. 1554-1564
Author(s):  
A G Frauman ◽  
P Chu ◽  
L C Harrison
Keyword(s):  
Major Histocompatibility Complex ◽  
Beta Cells ◽  
Mhc Class I ◽  
Pancreatic Beta Cells ◽  
Class I ◽  
General Mechanism ◽  
Major Histocompatibility ◽  
Cell Destruction ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules

The overexpression of major histocompatibility complex (MHC) class I molecules in endocrine epithelial cells is an early feature of autoimmune thyroid disease and insulin-dependent diabetes mellitus, which may reflect a cellular response, e.g., to viruses or toxins. Evidence from a transgenic model in pancreatic beta cells suggests that MHC class I overexpression could play an independent role in endocrine cell destruction. We demonstrate in this study that the transgenic overexpression of an allogeneic MHC class I protein (H-2Kb) linked to the rat thyroglobulin promoter, in H-2Kk mice homozygous for the transgene, leads to thyrocyte atrophy, hypothyroidism, growth retardation, and death. Thyrocyte atrophy occurred in the absence of lymphocytic infiltration. Tolerance to allogeneic class I was revealed by the reduced ability of primed lymphocytes from transgenic mice to lyse H-2Kb target cells in vitro. This nonimmune form of thyrocyte destruction and hypothyroidism recapitulates the beta-cell destruction and diabetes that results from transgenic overexpression of MHC class I molecules in pancreatic beta cells. Thus, we conclude that overexpression of MHC class I molecules may be a general mechanism that directly impairs endocrine epithelial cell viability.

scholarly journals H-2M3a violates the paradigm for major histocompatibility complex class I peptide binding.

1995 ◽  
Vol 181 (5) ◽  
pp. 1817-1825 ◽  
Author(s):  
J M Vyas ◽  
J R Rodgers ◽  
R R Rich
Keyword(s):  
Amino Acids ◽  
Mhc Class I ◽  
Temperature Shift ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Compensatory Adaptation ◽  
Chemotactic Peptides ◽  
The Stability ◽  
Formyl Peptides

The major histocompatibility (MHC) class I-b molecule H-2M3a binds and presents N-formylated peptides to cytotoxic T lymphocytes. This requirement potentially places severe constraints on the number of peptides that M3a can present to the immune system. Consistent with this idea, the M3a-Ld MHC class I chimera is expressed at very low levels on the cell surface, but can be induced significantly by the addition of specific peptides at 27 degrees C. Using this assay, we show that M3a binds many very short N-formyl peptides, including N-formyl chemotactic peptides and canonical octapeptides. This observation is in sharp contrast to the paradigmatic size range of peptides of 8-10 amino acids binding to most class I-a molecules and the class I-b molecule Qa-2. Stabilization by fMLF-benzyl amide could be detected at peptide concentrations as low as 100 nM. While N-formyl peptides as short as two amino acids in length stabilized expression of M3a-Ld, increasing the length of these peptides added to the stability of peptide-MHC complexes as determined by 27-37 degrees C temperature shift experiments. We propose that relaxation of the length rule may represent a compensatory adaptation to maximize the number of peptides that can be presented by H-2M3a.

scholarly journals Porcine major histocompatibility complex (MHC) class I molecules and analysis of their peptide-binding specificities

2011 ◽  
Vol 63 (12) ◽  
pp. 821-834 ◽  
Author(s):  
Lasse Eggers Pedersen ◽  
Mikkel Harndahl ◽  
Michael Rasmussen ◽  
Kasper Lamberth ◽  
William T. Golde ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Peptide Binding ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecules
Sign in / Sign up

Export Citation Format

Share Document