Dynamic membrane organization coordinates protein-O-mannosylation and proteostasis in mycobacteria
Abstract
Integral membrane enzymes operate within molecular environments, yet how these are organized remains poorly understood. Using M. smegmatis as a mycobacterial model, we define the membrane environment of the protein O-mannosyltransferase MtPMT through stratified interactomics combining affinity purification-mass spectrometry under four stringencies with a persistence score. This approach resolves a persistent membrane-associated core of 108 proteins from more transient layers, revealing a hierarchically organized landscape enriched in Sec protein translocation, protein biogenesis and envelope proteostasis machineries.
Reciprocal affinity purification and in vivo FRET identify YajC and FtsH as neighbors of MtPMT, while structural modelling supports integration within a Sec-associated assembly. Genetic disruption of factors reduces O-mannosylation activity, demonstrating dependence on platform integrity. The MtPMT-associated network is remodelled during growth, indicating an adaptive system. Loss of POM compromises envelope permeability and stress resilience, linking Omannosylation to fitness. Together, our results establish protein O-mannosylation as an integrated component of a dynamic membrane platform coordinating secretion, membrane protein biogenesis and proteostasis. Our findings support a model in which mycobacterial membranes contain specialized domains dynamically modulated by physiological state.
Related
- Post-assembly proteostasis of the respiratory chain is independent of respirasome organization
- Quality control at the Golgi couples membrane proteostasis to lipid metabolism
- COG5-mediated Golgi organization coordinates neural progenitor fate during human brain development
- NKCC1 coordinates SPAK–PP1 signalling to regulate KCC2 membrane stability and seizure susceptibility
- The nuclear membrane protein Samp1 links peripheral genome organization to the myogenic transcriptional program
BibTeX
@misc{riviere2026dynamic,
title = {{Dynamic membrane organization coordinates protein-O-mannosylation and proteostasis in mycobacteria}},
author = {Chloé Rivière and Gabriel Publicola and Alexandre Stella and Odile Burlet-Schiltz and Jérôme Nigou and Michel Rivière},
howpublished = {HAL},
year = {2026},
month = sep,
doi = {10.64898/2026.09.29.755281},
url = {https://hal.science/hal-05845083v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - UNPB
TI - Dynamic membrane organization coordinates protein-O-mannosylation and proteostasis in mycobacteria
AU - Chloé Rivière
AU - Gabriel Publicola
AU - Alexandre Stella
AU - Odile Burlet-Schiltz
AU - Jérôme Nigou
AU - Michel Rivière
PY - 2026
DA - 2026/09/29
PB - HAL
DO - 10.64898/2026.09.29.755281
UR - https://hal.science/hal-05845083v1
AB - Integral membrane enzymes operate within molecular environments, yet how these are organized remains poorly understood. Using M. smegmatis as a mycobacterial model, we define the membrane environment of the protein O-mannosyltransferase MtPMT through stratified interactomics combining affinity purification-mass spectrometry under four stringencies with a persistence score. This approach resolves a persistent membrane-associated core of 108 proteins from more transient layers, revealing a hierarchically organized landscape enriched in Sec protein translocation, protein biogenesis and envelope proteostasis machineries. Reciprocal affinity purification and in vivo FRET identify YajC and FtsH as neighbors of MtPMT, while structural modelling supports integration within a Sec-associated assembly. Genetic disruption of factors reduces O-mannosylation activity, demonstrating dependence on platform integrity. The MtPMT-associated network is remodelled during growth, indicating an adaptive system. Loss of POM compromises envelope permeability and stress resilience, linking Omannosylation to fitness. Together, our results establish protein O-mannosylation as an integrated component of a dynamic membrane platform coordinating secretion, membrane protein biogenesis and proteostasis. Our findings support a model in which mycobacterial membranes contain specialized domains dynamically modulated by physiological state.
ER -