The metazoan O-mannose (O-Man) glycoproteome is largely unknown. It has been shown that up to 30% of brain O-glycans are of the O-Man type, but essentially only alpha-dystroglycan (α-DG) of the dystrophin-glycoprotein complex is well characterized as an O-Man glycoprotein. Defects in O-Man glycosylation underlie congenital muscular dystrophies and considerable efforts have been devoted to explore this O-glycoproteome without much success. Here, we used our SimpleCell strategy using nuclease-mediated gene editing of a human cell line (MDA-MB-231) to reduce the structural heterogeneity of O-Man glycans and to probe the O-Man glycoproteome. In this breast cancer cell line we found that O-Man glycosylation is primarily found on cadherins and plexins on β-strands in extracellular cadherin and Ig-like, plexin and transcription factor domains. The positions and evolutionary conservation of O-Man glycans in cadherins suggest that they play important functional roles for this large group of cell adhesion glycoproteins, which can now be addressed. The developed O-Man SimpleCell strategy is applicable to most types of cell lines and enables proteome-wide discovery of O-Man protein glycosylation.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3876253 | PMC |
| http://dx.doi.org/10.1073/pnas.1313446110 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Global View of Domain-Specific O-Linked Mannose Glycosylation in Glycoengineered Cells.
Mol Cell Proteomics
July 2024
Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark. Electronic address:
Protein O-linked mannose (O-Man) glycosylation is an evolutionary conserved posttranslational modification that fulfills important biological roles during embryonic development. Three nonredundant enzyme families, POMT1/POMT2, TMTC1-4, and TMEM260, selectively coordinate the initiation of protein O-Man glycosylation on distinct classes of transmembrane proteins, including α-dystroglycan, cadherins, and plexin receptors. However, a systematic investigation of their substrate specificities is lacking, in part due to the ubiquitous expression of O-Man glycosyltransferases in cells, which precludes analysis of pathway-specific O-Man glycosylation on a proteome-wide scale.
View Article and Find Full Text PDFBrain-specific glycosylation enzyme GnT-IX maintains levels of protein tyrosine phosphatase receptor PTPRZ, thereby mediating glioma growth.
J Biol Chem
September 2023
Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan. Electronic address:
Gliomas are the most prevalent primary tumor of the central nervous system. Despite advances in imaging technologies, neurosurgical techniques, and radiotherapy, a cure for high-grade glioma remains elusive. Several groups have reported that protein tyrosine phosphatase receptor type Z (PTPRZ) is highly expressed in glioblastoma, and that targeting PTPRZ attenuates tumor growth in mice.
View Article and Find Full Text PDFThe importance of historically popular sires on the accuracy of genomic predictions of young animals in the US Holstein population.
JDS Commun
July 2023
Department of Animal and Dairy Science, University of Georgia, Athens 30602.
The dairy industry is known for its extensive use of artificial insemination, which has resulted in a population where most animals can be traced back to only a few sires. Due to their relatedness to the population, old influential sires could still contribute to the accuracy of genomic predictions. The objective of the study was to identify the impact of historically influential sires on the recent population.
View Article and Find Full Text PDFBrain-specific glycosylation of protein tyrosine phosphatase receptor type Z (PTPRZ) marks a demyelination-associated astrocyte subtype.
J Neurochem
August 2023
Department of Clinical Laboratory Sciences, School of Health Sciences, Fukushima Medical University, Fukushima, Japan.
Article Synopsis
- Astrocytes are the most common type of glial cells in the brain and have unique roles tied to their various subpopulations, particularly in relation to brain health and disease.
- A specific glycosylation of the PTPRZ protein, crucial for astrocyte function, is prevalent in reactive astrocytes during demyelination, but its role across different diseases has not been fully explored.
- Research shows that glycosylated PTPRZ is found in damaged brain areas of multiple sclerosis patients and in certain mouse models of demyelination, indicating that this modification is significant for the behavior and characteristics of astrocytes in disease contexts.
Dynamic Imine Bonding Facilitates Mannan Release from a Nanofibrous Peptide Hydrogel.
Bioconjug Chem
January 2023
Department of Bioengineering, Rice University, Houston, Texas77005, United States.
Recently, there has been increased interest in using mannan as an immunomodulatory bioconjugate. Despite notable immunological and functional differences between the reduced (R-Man) and oxidized (O-Man) forms of mannan, little is known about the impact of mannan oxidation state on its persistence or its potential controlled release from biomaterials that may improve immunotherapeutic or prophylactic efficacy. Here, we investigate the impact of oxidation state on the and release of mannan from a biocompatible and immunostimulatory multidomain peptide hydrogel, K(SL)K (abbreviated as K), that has been previously used for the controlled release of protein and small molecule payloads.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!