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Università della Svizzera italiana

How viruses hijack the ERAD tuning machinery

Noack, Julia ; Bernasconi, Riccardo ; Molinari, Maurizio

In: Journal of virology, 2014, vol. 88, no. 18, p. 10272-10275

An essential step during the intracellular life cycle of many positive-strand RNA viruses is the rearrangement of host cell membranes to generate membrane-bound replication platforms. For example, Nidovirales and Flaviviridae subvert the membrane of the endoplasmic reticulum (ER) for their replication. However, the absence of conventional ER and secretory pathway markers in virus-induced...

Università della Svizzera italiana

Division of labor among oxidoreductases : TMX1 preferentially acts on transmembrane polypeptides

Brambilla Pisoni, Giorgia ; Ruddock, Lloyd W. ; Bulleid, Neil ; Molinari, Maurizio

In: Molecular biology of the cell, 2015, vol. 26, no. 19, p. 3373-3556

The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins in eukaryotic cells. The lumen of the mammalian ER contains >20 members of the protein disulfide isomerase (PDI) superfamily, which ensure formation of the correct set of intramolecular and intermolecular disulfide bonds as crucial, rate-limiting reactions of the protein folding process. Components of...

Università della Svizzera italiana

A novel UGGT1 and p97-dependent checkpoint for native ectodomains with ionizable intramembrane residue

Merulla, Jessica ; Tatiana Soldà ; Maurizio Molinari

In: Molecular biology of the cell, 2015, vol. 26, no. 8, p. 1413-1574

Only native polypeptides are released from the endoplasmic reticulum (ER) to be transported at the site of activity. Persistently misfolded proteins are retained and eventually selected for ER-associated degradation (ERAD). The paradox of a structure- based protein quality control is that functional polypeptides may be destroyed if they are architecturally unfit. This has health-threatening...

Université de Fribourg

Reproduction, fat metabolism, and life span: what is the connection?

Hansen, Malene ; Flatt, Thomas ; Aguilaniu, Hugo

In: Cell Metabolism, 2013, vol. 17, no. 1, p. 10–19

Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part...

Université de Fribourg

Life-history evolution and the polyphenic regulation of somatic maintenance and survival

Flatt, Thomas ; Amdam, Gro V. ; Kirkwood, Thomas B. L. ; Omholt, Stig W.

In: The Quarterly Review of Biology, 2013, vol. 88, no. 3, p. 185–218

Here we discuss life-history evolution from the perspective of adaptive phenotypic plasticity, with a focus on polyphenisms for somatic maintenance and survival. Polyphenisms are adaptive discrete alternative phenotypes that develop in response to changes in the environment. We suggest that dauer larval diapause and its associated adult phenotypes in the nematode (Caenorhabditis elegans),...

Université de Fribourg

Reproduction of contagious caprine pleuropneumonia reveals the ability of convalescent sera to reduce hydrogen peroxide production in vitro

Liljander, Anne ; Sacchini, Flavio ; Stoffel, †, Michael H. ; Schieck, Elise ; Stokar‑Regenscheit, Nadine ; Labroussaa, Fabien ; Heller, Martin ; Salt, Jeremy ; Frey, Joachim ; Falquet, Laurent ; Goovaerts, Danny ; Jores, Joerg

In: Veterinary Research, 2019, vol. 50, no. 1, p. 10

Contagious caprine pleuropneumonia (CCPP), caused by Mycoplasma capricolum subsp. capripneumoniae is a severe disease widespread in Africa and Asia. Limited knowledge is available on the pathogenesis of this organism, mainly due to the lack of a robust in vivo challenge model and the means to do site-directed mutagenesis. This work describes the establishment of a novel caprine challenge...

Università della Svizzera italiana

Human IL-3/GM-CSF knock-in mice support human alveolar macrophage development and human immune responses in the lung

Willinger, Tim ; Rongvaux, Anthony ; Takizawa, Hitoshi ; Yancopoulos, George D. ; Valenzuela, David M. ; Murphy, Andrew J. ; Auerbach, Wojtek ; Eynon, Elizabeth E. ; Stevens, Sean ; Manz, Markus G. ; Flavell, Richard A.

In: Proceedings of the national academy of sciences of the United States of America, 2011, vol. 108, no. 6, p. 2390-2395

Mice with a functional human immune system have the potential to allow in vivo studies of human infectious diseases and to enable vaccine testing. To this end, mice need to fully support the development of human immune cells, allow infection with human pathogens, and be capable of mounting effective human immune responses. A major limitation of humanized mice is the poor development and...

Università della Svizzera italiana

Mitochondrial dysfunction induced by a SH2 domain-targeting STAT3 inhibitor leads to metabolic synthetic lethality in cancer cells

Genini, Davide ; Brambilla, Lara ; Laurini, Erik ; Merulla, Jessica ; Civenni, Gianluca ; Pandit, Shusil ; D'Antuono, Rocco ; Perez, Laurent ; Levy, David E. ; Pricl, Sabrina ; Carbone, Giuseppina M. ; Catapano, Carlo V.

In: Proceedings of the national academy of sciences of the United States of America, 2017, vol. 114, no. 25, p. E4924-E4933

In addition to its canonical role in nuclear transcription, signal transducer and activator of transcription 3 (STAT3) is emerging as an important regulator of mitochondrial function. Here, we demonstrate that a novel inhibitor that binds with high affinity to the STAT3 SH2 domain triggers a complex cascade of events initiated by interference with mitochondrial STAT3 (mSTAT3). The...

Università della Svizzera italiana

Molecular dynamics simulations with replica-averaged structural restraints generate structural ensembles according to the maximum entropy principle

Cavalli, Andrea ; Camilloni, Carlo ; Vendruscolo, Michele

In: The journal of chemical physics, 2013, vol. 138, no. 9, p. 094112

In order to characterise the dynamics of proteins, a well-established method is to incorporate experimental parameters as replica-averaged structural restraints into molecular dynamics simulations. Here, we justify this approach in the case of interproton distance information provided by nuclear Overhauser effects by showing that it generates ensembles of conformations according to the maximum...

Università della Svizzera italiana

CXCR7 prevents excessive CXCL12-mediated downregulation of CXCR4 in migrating cortical interneurons

Abe, Philipp ; Mueller, Wiebke ; Schütz, Dagmar ; MacKay, Fabienne ; Thelen, Marcus ; Zhang, Penglie ; Stumm, Ralf

In: Development, 2014, vol. 141, no. 9, p. 1857-1863

The CXCL12/CXCR4 signaling pathway is involved in the development of numerous neuronal and non-neuronal structures. Recent work established that the atypical second CXCL12 receptor, CXCR7, is essential for the proper migration of interneuron precursors in the developing cerebral cortex. Two CXCR7-mediated functions were proposed in this process: direct modulation of β-arrestin-mediated...