The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 8, 2024

Abstract Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis largely dictated by plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind ubiquitin conjugation machinery (E2~Ub) activate kinase activity. However, cellular targets of remain elusive despite years extensive efforts. Here we show unbiased phosphoproteomics that major target CAND1, regulatory protein controlling assembly cullin-RING ligases (CRLs). CAND1 phosphorylation weakens interaction with cullins, which expected impact large panel CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in ubiquitination landscape when introduced. Notably, promotes class cytoskeletal proteins called septins, thereby inhibiting formation cage-like structures encircling cytosolic bacteria. Overall, demonstrate pathogens have evolved an elaborate strategy modulate host signaling evade septin-cage entrapment.

Language: Английский

---

Soft X-ray Microscopy in Cell Biology: Current Status, Contributions and Prospects

Acta Naturae, Journal Year: 2024, Volume and Issue: 15(4), P. 32 - 43

Published: Jan. 17, 2024

The recent advances achieved in microscopy technology have led to a significant breakthrough biological research. Super-resolution fluorescent now allows us visualize subcellular structures down the pin-pointing of single molecules them, while modern electron has opened new possibilities study protein complexes their native, intracellular environment at near-atomic resolution. Nonetheless, both and remained beset by principal shortcomings: reliance on labeling procedures severe sample volume limitations, respectively. Soft X-ray is candidate method that can compensate for shortcomings technologies making possible observation entirety cellular interior without chemical fixation with an isotropic resolution 40-70 nm. This will thus bridge gap between light (although this being narrowed, it still exists) resolve issue compatibility former, possibly near future, latter methods. review aims assess current state soft its impact our understanding organization. It also attempts look into future microscopy, particularly as relates seamless integration cell biology toolkit.

Language: Английский

---

The great escape: a Shigella effector unlocks the septin cage

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 15, 2024

Shigella, an important human pathogen, can secrete effector proteins to invade host cells and evade mechanisms of cell-autonomous immunity. In a new manuscript published in Nature Communications, Xian et al. report that the Shigella kinase OspG promotes ubiquitination septin cytoskeletal cage entrapment.

Language: Английский

---

First person – Damián Lobato-Márquez and José Javier Conesa

Journal of Cell Science, Journal Year: 2023, Volume and Issue: 136(7)

Published: April 1, 2023

ABSTRACT First Person is a series of interviews with the first authors selection papers published in Journal Cell Science, helping researchers promote themselves alongside their papers. Damián Lobato-Márquez and José Javier Conesa are co-first on ‘ Septins K63 ubiquitin chains present separate bacterial microdomains during autophagy entrapped Shigella’, JCS. Research fellow lab Serge Mostowy at London School Hygiene Tropical Medicine, London, UK, investigating pathogenesis cell-autonomous immune response. postdoctoral research assistant Jose María Valpuesta CNB-CSIC, Madrid, Spain, where he works structural biology method development.

Language: Английский

---

Interplay between septins and ubiquitin-mediated xenophagy during Shigella entrapment

Autophagy Reports, Journal Year: 2023, Volume and Issue: 2(1)

Published: May 17, 2023

Septins are cytoskeletal proteins implicated in numerous cellular processes including cytokinesis and morphogenesis. In the case of infection by Shigella flexneri, septins assemble into cage-like structures that entrap cytosolic bacteria targeted autophagy. The interplay between septin cage entrapment bacterial autophagy is poorly understood. We used a correlative light cryo-soft X-ray tomography (cryo-SXT) pipeline to study its near-native state. Septin cages could be identified as dense structures, indicating they contain host cell lipids consistent with their links. Airyscan confocal microscopy Shigella-septin showed lysine 63 (K63)-linked ubiquitin chains present separate microdomains, suggesting recruited separately. Finally, Cryo-SXT live-cell imaging revealed an interaction microtubule-associated protein chain 3B (LC3B)-positive membranes during Shigella. Collectively our data new model for how septin-caged

Language: Английский

---