Inhibition of hostN-myristoylation compromises the infectivity of SARS-CoV-2 due to Golgi-bypassing egress from lysosomes and endoplasmic reticulum DOI Creative Commons

Saber H. Saber,

Mohammed R. Shaker,

Julian Sng

et al.

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

Published: March 3, 2023

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which caused the disease 2019 (COVID-19) pandemic, remains a global health concern despite vaccines, neutralizing antibodies, and antiviral drugs. Emerging mutations can reduce effectiveness of these treatments, suggesting that targeting host cell factors may be valuable alternative. N -myristoyltransferases (NMT) are essential enzymes for protein -myristoylation, affecting stability, interaction, localization, function numerous proteins. We demonstrate selective inhibition NMT decreases SARS-CoV-2 infection by 90% in human lung primary nasal epithelial cells, choroid plexus-cortical neuron organoids. does not affect viral entry, replication or release, but impairs maturation incorporation envelope proteins into newly assembled virions, leading to compromised infectivity released virions. The triggers Golgi-bypassing pathway progeny virion egress, occurs through endoplasmic reticulum lysosomal intermediates.

Language: Английский

Role of TMEM230 in the Aberrant Glycosylation in Human Autoimmunity and Cancer DOI Creative Commons
Elena Angeli, Cinzia Cocola, Edoardo Abeni

et al.

Proteoglycan Research, Journal Year: 2025, Volume and Issue: 3(1)

Published: Jan. 1, 2025

ABSTRACT Alterations in glycoconjugate profiles are thought to promote changes cell‐to‐cell and cell‐to‐intracellular extracellular scaffold interactions human disease. The nearly unlimited number of “glycoforms” that may exist nature difficult study due glycosylation modifications being associated with non‐genome coded posttranscription post‐translation processes. Specific products generated by dependent on concentration sub‐cellular locations glycan synthesis processing enzymes. An indirect “high‐throughput” approach is characterize enzymes (hydrolases transferases) single cell sequencing all types tissue diseases. We previously identified TMEM230 as an endoplasmic reticulum (ER) protein regulates NOTCH glycoprotein receptor ligand signaling zebrafish blood vessel formation destructive remodeling capacities diverse including fibroblast, phagocytic immune system cells patients cancer or granulomatous systemic vasculitis autoimmune disorder. represents a paradigm mediated signal transduction supports the role modifications. ER initiates earliest steps synthesis, sorting, trafficking. As remodeling, Notch hallmarks disorders, we investigated whether aberrant expression was also rheumatoid arthritis (RA). In this current study, analysis supported downregulated synovial RA while were predominantly upregulated. contrast, upregulated high‐grade compared low‐grade gliomas it N‐linked (GlcNAc), glycosaminoglycan expression. Our collective results support glycan/glycoconjugate aggressive gliomas. therefore be therapeutic target marker for clinical treatment induced autoimmunity disorders cancer.

Language: Английский

Citations

1

The Essential Functions of Molecular Chaperones and Folding Enzymes in Maintaining Endoplasmic Reticulum Homeostasis DOI
Linda M. Hendershot, Teresa M. Buck, Jeffrey L. Brodsky

et al.

Journal of Molecular Biology, Journal Year: 2023, Volume and Issue: 436(14), P. 168418 - 168418

Published: Dec. 22, 2023

Language: Английский

Citations

18

Vacuolar Degradation of Plant Organelles DOI
Marisa S. Otegui, Charlotte Steelheart, Wenlong Ma

et al.

The Plant Cell, Journal Year: 2024, Volume and Issue: 36(9), P. 3036 - 3056

Published: April 24, 2024

Plants continuously remodel and degrade their organelles due to damage from metabolic activities environmental stressors, as well an integral part of cell differentiation programs. Whereas certain use local hydrolytic enzymes for limited remodeling, most the pathways that control partial or complete dismantling rely on vacuolar degradation. Specifically, selective autophagic play a crucial role in recognizing sorting plant organelle cargo clearance, especially under cellular stress conditions induced by factors like heat, drought, damaging light. In these short reviews, we discuss mechanisms degradation chloroplasts, mitochondria, endoplasmic reticulum, Golgi, peroxisomes, with emphasis autophagy, recently discovered autophagy receptors organelles, crosstalk other catabolic pathways.

Language: Английский

Citations

7

ER-to-lysosome-associated degradation acts as failsafe mechanism upon ERAD dysfunction DOI

Elisa Fasana,

Ilaria Fregno,

Carmela Galli

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(6), P. 2773 - 2785

Published: May 21, 2024

Language: Английский

Citations

6

Refining S-acylation: Structure, regulation, dynamics, and therapeutic implications DOI Creative Commons
Muhammad Anwar, Gijs R. van den Brink

The Journal of Cell Biology, Journal Year: 2023, Volume and Issue: 222(11)

Published: Sept. 27, 2023

With a limited number of genes, cells achieve remarkable diversity. This is to large extent achieved by chemical posttranslational modifications proteins. Amongst these are the lipid that have unique ability confer hydrophobicity. The last decade has revealed proteins extremely frequent and affect great variety cellular pathways physiological processes. particularly true for S-acylation, only reversible modification. enzymes involved in S-acylation deacylation starting be understood, list undergo this modification ever-increasing. We will describe state knowledge on regulate from their structure regulation, how influences target proteins, finally offer perspective alterations balance between may contribute disease.

Language: Английский

Citations

14

Trafficking of K63-polyubiquitin modified membrane proteins in a macroautophagy-independent pathway is linked to ATG9A DOI Open Access
Francesco Scavone,

Sharon Lian,

Eeva‐Liisa Eskelinen

et al.

Molecular Biology of the Cell, Journal Year: 2025, Volume and Issue: 36(4)

Published: Feb. 19, 2025

Cytoplasmic K63-linked polyubiquitin signals have well-established roles in endocytosis and selective autophagy. However, how these help to direct different cargos intracellular trafficking routes is unclear. Here we report that, when the K63-polyubiquitin signal blocked by expression of a high-affinity sensor (named Vx3), many proteins originating from plasma membrane are found trapped clusters small vesicles that colocalize with ATG9A, transmembrane protein plays an essential role Importantly, whereas ATG9A required for cluster formation, other core autophagy machinery as well cargo receptors not required. Although sequestered vesicular ATG9-dependent manner, additional needed induce LC3 conjugation. Upon removal Vx3 block, K63-polyubiquitylated rapidly delivered lysosomes. These observations suggest unexpected K63-polyubiquitin–modified proteins.

Language: Английский

Citations

0

Lysosomal degradation of ER client proteins by ER-phagy and related pathways DOI Creative Commons
Carla Salomo-Coll, Natalia Jiménez-Moreno, Simon Wilkinson

et al.

Journal of Molecular Biology, Journal Year: 2025, Volume and Issue: unknown, P. 169035 - 169035

Published: Feb. 1, 2025

The endoplasmic reticulum (ER) is a major site of cellular protein synthesis. Degradation overabundant, misfolded, aggregating or unwanted proteins required to maintain proteostasis and avoid the deleterious consequences aberrant accumulation, at organismal level. While extensive research has shown an important role for proteasomally-mediated, ER-associated degradation (ERAD) in maintaining proteostasis, it becoming clear that there substantial lysosomal "client" from ER lumen membrane (ER-to-lysosome degradation, ERLAD). Here we provide brief overview broad categories ERLAD - predominantly ER-phagy (ER autophagy) pathways related processes. We collate client known date, either individual species proteins. Where known, summarise molecular mechanisms by which they are selected setting client(s) correct cell tissue function. Finally, highlight questions remain open this area.

Language: Английский

Citations

0

Glycosylation Regulation by TMEM230 in Aging and Autoimmunity DOI Open Access
Eleonora Piscitelli, Edoardo Abeni,

Cristiana Balbino

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(6), P. 2412 - 2412

Published: March 7, 2025

Aging is often a choice between developing cancer or autoimmune disorders, due in part to loss of self-tolerance immunological recognition rogue-acting tumor cells. Self-tolerance and cell by the immune system are processes very much dependent on specific signatures glycans glycosylated factors present plasma membrane stromal components tissue. Glycosylated generated nearly innumerable variations nature, allowing for immensely diverse role these aging flexibility necessary cellular interactions tissue functionality. In previous studies, we showed that differential expression TMEM230, an endoplasmic reticulum (ER) protein was associated with enzymes regulating glycan synthesis processing glycosylation rheumatoid arthritis synovial using single-cell transcript sequencing. this current study, characterize genes pathways co-modulated all types processing, as well glycosylation. Genes biological molecular hallmarks were mitochondria-dependent oxidative phosphorylation reactive oxygen species synthesis, ER-dependent stress unfolded response, DNA repair (UV response P53 signaling pathways), senescence, glycolysis apoptosis regulation through PI3K-AKT-mTOR have been shown play important roles neurodegeneration (such Parkinson’s Alzheimer’s disease). We propose downregulation TMEM230 RNASET2 may represent paradigm study age-dependent disorders their glycosylation, signaling.

Language: Английский

Citations

0

ER-to-lysosome-associated degradation DOI
Maurizio Molinari

Current Biology, Journal Year: 2025, Volume and Issue: 35(9), P. R320 - R322

Published: May 1, 2025

Language: Английский

Citations

0

Transmembrane protein TMEM230, regulator of metalloproteins and motor proteins in gliomas and gliosis DOI
Cinzia Cocola, Edoardo Abeni,

Valentina Martino

et al.

Advances in protein chemistry and structural biology, Journal Year: 2024, Volume and Issue: unknown, P. 255 - 297

Published: Jan. 1, 2024

Language: Английский

Citations

2