Système endomembranaire

Résumé

Le système endomembranaire se compose des différentes membranes internes qui sont en suspension dans le cytoplasme d'une cellule eucaryote. Ces membranes divisent la cellule en compartiments fonctionnels et structurels appelés organites. Chez les eucaryotes, les organites du système endomembranaire comprennent : la partie externe de la membrane nucléaire, le réticulum endoplasmique, l'appareil de Golgi, les lysosomes, les vacuoles, les vésicules et des endosomes. Le système se définit plus précisément comme l'ensemble des membranes qui forment une continuité fonctionnelle, soit en étant connectées directement entre elles, soit en échangeant de la matière à travers le transport vésiculaire. À cet égard, il convient de noter que le système endomembranaire n'inclut pas les membranes des mitochondries, des peroxysomes et des chloroplastes. L'enveloppe nucléaire est constituée d'une double bicouche lipidique — une membrane interne et une membrane externe — enveloppant le noyau. Le réticu

Source officielle

https://fr.wikipedia.org/wiki/Syst%C3%A8me_endomembranaire

À propos de ce résultat

Cette page est générée automatiquement et peut contenir des informations qui ne sont pas correctes, complètes, à jour ou pertinentes par rapport à votre recherche. Il en va de même pour toutes les autres pages de ce site. Veillez à vérifier les informations auprès des sources officielles de l'EPFL.

Publications associées (21)

Publications associées

Chargement

Personnes associées (3)

Personnes associées

Chargement

Unités associées (3)

Unités associées

Chargement

Concepts associés (28)

Concepts associés

Chargement

Cours associés (15)

Cours associés

Chargement

Séances de cours associées (28)

Séances de cours associées

Chargement

, , , , , , , , ,

Acyl protein thioesterase APT2 interacts with membranes via its charged beta-tongue, becomes palmitoylated by ZDHHC3/7 and deforms the bilayer to extract substrate acyl chains. APT2 deacylation leads to its membrane release and degradation. Many biochemical reactions require controlled recruitment of proteins to membranes. This is largely regulated by posttranslational modifications. A frequent one is S-acylation, which consists of the addition of acyl chains and can be reversed by poorly understood acyl protein thioesterases (APTs). Using a panel of computational and experimental approaches, we dissect the mode of action of the major cellular thioesterase APT2 (LYPLA2). We show that soluble APT2 is vulnerable to proteasomal degradation, from which membrane binding protects it. Interaction with membranes requires three consecutive steps: electrostatic attraction, insertion of a hydrophobic loop and S-acylation by the palmitoyltransferases ZDHHC3 or ZDHHC7. Once bound, APT2 is predicted to deform the lipid bilayer to extract the acyl chain bound to its substrate and capture it in a hydrophobic pocket to allow hydrolysis. This molecular understanding of APT2 paves the way to understand the dynamics of APT2-mediated deacylation of substrates throughout the endomembrane system.

NATURE RESEARCH2021

Chargement

Staphylococcus aureusis an opportunistic pathogen that can grow in a wide array of conditions: on abiotic surfaces, on the skin, in the nose, in planktonic or biofilm forms and can cause many type of infections. Consequently,S.aureusmust be able to adapt rapidly to these changing growth conditions, an ability largely driven at the posttranscriptional level. RNA helicases of the DEAD-box family play an important part in this process. In particular, CshA, which is part of the degradosome, is required for the rapid turnover of certain mRNAs and its deletion results in cold-sensitivity. To understand the molecular basis of this phenotype, we conducted a large genetic screen isolating 82 independent suppressors of cold growth. Full genome sequencing revealed the fatty acid synthesis pathway affected in many suppressor strains. Consistent with that result, sublethal doses of triclosan, a FASII inhibitor, can partially restore growth of acshAmutant in the cold. Overexpression of the genes involved in branched-chain fatty acid synthesis was also able to suppress the cold-sensitivity. Using gas chromatography analysis of fatty acids, we observed an imbalance of straight and branched-chain fatty acids in thecshAmutant, compared to the wild-type. This imbalance is compensated in the suppressor strains. Thus, we reveal for the first time that the cold sensitive growth phenotype of a DEAD-box mutant can be explained, at least partially, by an improper membrane composition. The defect correlates with an accumulation of the pyruvate dehydrogenase complex mRNA, which is inefficiently degraded in absence of CshA. We propose that the resulting accumulation of acetyl-CoA fuels straight-chained fatty acid production at the expense of the branched ones. Strikingly, addition of acetate into the medium mimics thecshAdeletion phenotype, resulting in cold sensitivity suppressed by the mutations found in our genetic screen or by sublethal doses of triclosan. Author summary DEAD-box RNA helicases are highly conserved proteins found in all domains of life. By acting on RNA secondary structures they determine the fate of RNA from transcription to degradation. Bacterial DEAD-box RNA helicases are not essential under laboratory conditions but are required for fitness and under stress conditions. Whereas many DEAD-box protein mutants display a cold sensitive phenotype, the underlying mechanisms have been studied only in few cases and found to be associated with ribosome biogenesis. We aimed here to elucidate the cold sensitivity of acshAmutant in the Gram-positive opportunist pathogenStaphylococcus aureus. Our study revealed for the first time that part of the cold sensitivity is related to the inability of the bacterium to adapt the cytoplasmic membrane to lower temperatures. We propose that straight-chain fatty acid synthesis, reduced to sustain growth at lower temperature, is maintained due to inefficient turn-over of the pyruvate dehydrogenase mRNA, leading to elevated acetyl-CoA levels. This study allowed us to unravel at least in part the cold sensitive phenotype and to show that the pyruvate dehydrogenase activity plays an important function in the regulation of fatty acid composition of the membrane, a process that remains poorly understood in Gram-positive bacteria.

PUBLIC LIBRARY SCIENCE2020

Chargement

Drug-induced increase in lysobisphosphatidic acid reduces the cholesterol overload in Niemann-Pick type C cells and mice

Marc Moniatte, Jonathan Paz Montoya

Most cells acquire cholesterol by endocytosis of circulating low-density lipoproteins (LDLs). After cholesteryl ester de-esterification in endosomes, free cholesterol is redistributed to intracellular membranes via unclear mechanisms. Our previous work suggested that the unconventional phospholipid lysobisphosphatidic acid (LBPA) may play a role in modulating the cholesterol flux through endosomes. In this study, we used the Prestwick library of FDA-approved compounds in a high-content, image-based screen of the endosomal lipids, lysobisphosphatidic acid and LDL-derived cholesterol. We report that thioperamide maleate, an inverse agonist of the histamine H3 receptor HRH3, increases highly selectively the levels of lysobisphosphatidic acid, without affecting any endosomal protein or function that we tested. Our data also show that thioperamide significantly reduces the endosome cholesterol overload in fibroblasts from patients with the cholesterol storage disorder Niemann-Pick type C (NPC), as well as in liver of Npc1(-/-) mice. We conclude that LBPA controls endosomal cholesterol mobilization and export to cellular destinations, perhaps by fluidifying or buffering cholesterol in endosomal membranes, and that thioperamide has repurposing potential for the treatment of NPC.

2019

Chargement

PUBLIC LIBRARY SCIENCE2020