N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine DOI Open Access
Chuchu Wang, Chunyu Zhao, Xiao Hu

et al.

Published: Sept. 13, 2024

Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, amyloid aggregation. However, how PTMs regulate function presynaptic terminals remains unclear. Previously, we reported that clusters synaptic vesicles (SV) 1 , neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering 2 . Here, based on our previous findings, further demonstrate N-terminal acetylation, which occurs under physiological conditions is irreversible mammalian cells, significantly enhances the functional activity SVs. Mechanistic studies reveal enhancement caused by N-acetylation-promoted insertion α-syn’s N-terminus increased intermolecular interactions LPC-containing membrane. Our work demonstrates N-acetylation fine-tunes α-syn–LPC interaction for mediating SV clustering.

Language: Английский

Mass Spectrometry Strategies for O-Glycoproteomics DOI Creative Commons
Amanda Helms, Jennifer S. Brodbelt

Cells, Journal Year: 2024, Volume and Issue: 13(5), P. 394 - 394

Published: Feb. 25, 2024

Glycoproteomics has accelerated in recent decades owing to numerous innovations the analytical workflow. In particular, new mass spectrometry strategies have contributed inroads O-glycoproteomics, a field that lags behind N-glycoproteomics due several unique challenges associated with complexity of O-glycosylation. This review will focus on progress sample preparation, enrichment strategies, and MS/MS techniques for identification characterization O-glycoproteins.

Language: Английский

Citations

3
Comprehensive O-Glycan Analysis by Porous Graphitized Carbon Nanoliquid Chromatography–Mass Spectrometry DOI Creative Commons
Tao Zhang, Wenjun Wang, Manfred Wuhrer

et al.

Analytical Chemistry, Journal Year: 2024, Volume and Issue: 96(22), P. 8942 - 8948

Published: May 17, 2024

The diverse and unpredictable structures of

Language: Английский

Citations

3
Clinical glycoproteomics: methods and diseases DOI Creative Commons
Yujia Wang,

Kaixin Lei,

Lijun Zhao

et al.

MedComm, Journal Year: 2024, Volume and Issue: 5(10)

Published: Oct. 1, 2024

Abstract Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural functional changes glycoprotein, which is closely related the occurrence development diseases. Consequently, exploring protein can shed light on mechanisms behind disease manifestation pave way for innovative diagnostic therapeutic strategies. Nonetheless, study clinical glycoproteomics fraught with challenges due low abundance intricate structures glycosylation. Recent advancements mass spectrometry‐based have improved our ability identify abnormal glycoproteins samples. In this review, we aim provide comprehensive overview foundational principles recent glycoproteomic methodologies applications. Furthermore, discussed typical characteristics, underlying functions, diseases, brain cardiovascular cancers, kidney metabolic Additionally, highlighted potential avenues future glycoproteomics. These insights provided review will enhance comprehension methods diseases promote elucidation pathogenesis discovery novel biomarkers targets.

Language: Английский

Citations

3
N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine DOI Creative Commons
Chuchu Wang, Chunyu Zhao,

Xiao Hu

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: April 19, 2024

Previously, we reported that α-synuclein (α-syn) clusters synaptic vesicles (SV) Diao et al., 2013, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering Lai 2023. Meanwhile, post-translational modifications (PTMs) of α-syn such as acetylation phosphorylation play important yet distinct roles in regulating conformation, membrane binding, amyloid aggregation. However, how PTMs regulate function presynaptic terminals remains unclear. Here, based on our previous findings, further demonstrate N-terminal acetylation, which occurs under physiological conditions is irreversible mammalian cells, significantly enhances the functional activity SVs. Mechanistic studies reveal enhancement caused by N-acetylation-promoted insertion α-syn’s N-terminus increased intermolecular interactions LPC-containing membrane. N-acetylation work shown to fine-tune interaction between LPC, mediating role vesicle clustering.

Language: Английский

Citations

2
O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma DOI Creative Commons
Jie Li, Wen Zhou, Jianzhi Zhang

et al.

Fundamental Research, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

The intracellular O-linked N-acetylglucosamine (O-GlcNAc) glycosylation mediates many signal transduction events and regulates tumorigenesis. Previously the RNA N6-methyladenosine (m6A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), has been shown to be O-GlcNAcylated on Ser-263 during Hepatitis B virus (HBV) infection promote HBV-related hepatocellular carcinoma. Herein we mapped YTHDF2 O-GlcNAcylation at Thr-49 via electron-transfer dissociation mass spectrometry under unperturbed conditions. We show that antagonizes Extracellular-signal regulated kinase (ERK)-dependent phosphorylation Ser-39 promotes degradation. downstream signaling pathway of in lung carcinoma is thus upregulated, which leads downregulation c-Myc. further used mouse xenograft models YTHDF2-T49A mutants increased cancer size. Our work reveals a key role tumorigenesis suggests exerts distinct functions different biological stress.

Language: Английский

Citations

2
Synthesis of Bodipy-Tagged Galactoconjugates and Evaluation of Their Antibacterial Properties DOI Creative Commons
Chiara M. A. Gangemi,

Maura Monforte,

Antonino Arrigo

et al.

Molecules, Journal Year: 2024, Volume and Issue: 29(10), P. 2299 - 2299

Published: May 14, 2024

As a development of our research on biocompatible glycoconjugate probes and specifically multi-chromophoric systems, herein, we report the synthesis early bactericidal tests two luminescent glycoconjugates whose basic structure is characterized by boron dipyrromethene difluoride (BODIPY) moieties three galactoside rings mounted an oligophenylene ethynylene (OPE) skeleton. BODIPY fluorophores have found widespread application in many branches biology last few decades. In particular, molecular platforms showing different groups unique photophysical behavior useful fluorescence imaging. Construction complex architecture new accomplished through convergent route that exploits series copper-free Heck-Cassar-Sonogashira cross-couplings. The great emergency due to proliferation bacterial infections, conjunction with growing antibiotic resistance, requires production multifunctional drugs efficient methods for their targeted delivery control bacteria-associated diseases. Preliminary studies properties as antibacterial agents against representatives Gram-negative (

Language: Английский

Citations

1
N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine DOI Creative Commons
Chuchu Wang, Chunyu Zhao,

Xiao Hu

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Dec. 27, 2024

Previously, we reported that α-synuclein (α-syn) clusters synaptic vesicles (SV) Diao et al., 2013, and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering Lai 2023. Meanwhile, post-translational modifications (PTMs) of α-syn such as acetylation phosphorylation play important yet distinct roles in regulating conformation, membrane binding, amyloid aggregation. However, how PTMs regulate function presynaptic terminals remains unclear. Here, based on our previous findings, further demonstrate N-terminal acetylation, which occurs under physiological conditions is irreversible mammalian cells, significantly enhances the functional activity SVs. Mechanistic studies reveal enhancement caused by N-acetylation-promoted insertion α-syn’s N-terminus increased intermolecular interactions LPC-containing membrane. N-acetylation work shown to fine-tune interaction between LPC, mediating role vesicle clustering.

Language: Английский

Citations

1
O-GlcNAcylation of YTHDF2 antagonizes ERK-dependent phosphorylation and inhibits lung carcinoma DOI Open Access
Jie Li, Wen Zhou, Jianzhi Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Sept. 10, 2023

SUMMARY The intracellular O-linked N-acetylglucosamine (O-GlcNAc) glycosylation mediates many signal transduction events and regulates tumorigenesis. Previously the RNA N6-methyladenosine (m 6 A) reader, YTH (YT521-B homology) domain 2 (YTHDF2), has been shown to be O-GlcNAcylated on Ser-263 during Hepatitis B virus (HBV) infection promote HBV-related hepatocellular carcinoma. Herein we mapped YTHDF2 O-GlcNAcylation at Thr-49 via electron-transfer dissociation mass spectrometry under unperturbed conditions. We show that antagonizes Extracellular-signal regulated kinase (ERK)-dependent phosphorylation Ser-39 promotes degradation. downstream signaling pathway of in lung carcinoma are thus upregulated, which leads downregulation c-Myc. further used mouse xenograft models YTHDF2-T49A mutants increased cancer size. Our work reveals a key role tumorigenesis suggests exerts distinct functions different biological stress.

Language: Английский

Citations

2
O-GlcNAc regulates YTHDF1 and YTHDF3 activity DOI
Mary W. N. Burns, Jennifer J. Kohler

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(11), P. 1570 - 1572

Published: Nov. 1, 2023

Language: Английский

Citations

2
A Patching and Coding Lipid Raft-Localized Universal Imaging Platform DOI Creative Commons

Tong Zhong,

Younan Chen,

Xiaomin Yan

et al.

Chemical & Biomedical Imaging, Journal Year: 2023, Volume and Issue: 2(2), P. 135 - 146

Published: Nov. 29, 2023

Lipid rafts (LRs) are relatively well-ordered functional microdomains in cell membranes and play an irreplaceable role physiological processes as a transduction platform for multiple signaling pathways. Due to their small size high spatiotemporal dynamics, it is difficult perform lipid raft-localized biomolecule imaging on the surface of living cells. Here, we report DNA nanotechnology-based reversible manipulation localized analysis rafts, which consists two modules: “patching coding probe pair” “fishing probe”. The pair generated by modifying different sets connectable structures raft-specific protein. After recognizing probes close proximity linked ligase reaction form raft identity (LR-ID) code. LR-ID strand patches stabilizes structure. Interestingly, formed can be depatched restriction endonucleases, providing first structure We also designed probe” with hairpin using aptamer that specifically bind target. cascade input signals “LR-ID” “target protein” generate “off–on” fluorescence switch, allowing dynamic monitoring target proteins rafts. By encoding arbitrary targets (in case glycans) have created universal platform. This work provides integrated analytical manipulative reveal associated pathways at molecular level.

Language: Английский

Citations

2