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Université de Fribourg

In vivo function of the lipid raft protein flotillin-1 during cd8+ t cell–mediated host surveillance

Ficht, Xenia ; Ruef, Nora ; Stolp, Bettina ; Samson, Guerric P. B. ; Moalli, Federica ; Page, Nicolas ; Merkler, Doron ; Nichols, Ben J. ; Diz-Muñoz, Alba ; Legler,, Daniel F. ; Niggli, Verena

In: The Journal of Immunology, 2019, p. -

Flotillin-1 (Flot1) is an evolutionary conserved, ubiquitously expressed lipid raft– associated scaffolding protein. Migration of Flot1-deficient neutrophils is impaired because of a decrease in myosin II–mediated contractility. Flot1 also accumulates in the uropod of polarized T cells, suggesting an analogous role in T cell migration. In this study, we analyzed morphology and migration...

Public access from May 14, 2020
Università della Svizzera italiana

Proteasomal and lysosomal clearance of faulty secretory proteins : ER-associated degradation (ERAD) and ER-to-lysosome-associated degradation (ERLAD) pathways

Fregno, Ilaria ; Molinari, Maurizio

In: Critical reviews in biochemistry and molecular biology, 2019, vol. 54, no. 2, p. 153-163

About 40% of the eukaryotic cell’s proteins are inserted co- or post-translationally in the endoplasmic reticulum (ER), where they attain the native structure under the assistance of resident molecular chaperones and folding enzymes. Subsequently, these proteins are secreted from cells or are transported to their sites of function at the plasma membrane or in organelles of the secretory and ...

Università della Svizzera italiana

ESCRT-III-driven piecemeal micro-ER-phagy remodels the ER during recovery from ER stress

Loi, Marisa ; Raimondi, Andrea ; Morone, Diego ; Molinari, Maurizio

In: Nature communications, 2019, vol. 10, p. 5058

The endoplasmic reticulum (ER) produces about 40% of the nucleated cell’s proteome. ER size and content in molecular chaperones increase upon physiologic and pathologic stresses on activation of unfolded protein responses (UPR). On stress resolution, the mammalian ER is remodeled to pre-stress, physiologic size and function on activation of the LC3-binding activity of the translocon...

Università della Svizzera italiana

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

Volpi, Vera G. ; Ferri, Cinzia ; Fregno, Ilaria ; Del Carro, Ubaldo ; Bianchi, Francesca ; Scapin, Cristina ; Pettinato, Emanuela ; Solda, Tatiana ; Feltri, M. Laura ; Molinari, Maurizio ; Wrabetz, Lawrence ; D’Antonio, Maurizio

In: PLOS genetics, 2019, vol. 15, no. 4, p. e1008069

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the...

Università della Svizzera italiana

Identification of a novel non-desmoglein autoantigen in Pemphigus Vulgaris

Di Lullo, Giulia ; Calabresi, Valentina ; Mariotti, Feliciana ; Zambruno, Giovanna ; Lanzavecchia, Antonio ; Di Zenzo, Giovanni

In: Frontiers in immunology, 2019, vol. 10, p. 1391

Pemphigus vulgaris (PV) is an autoimmune bullous disease of the skin and mucous membranes characterized by the presence of circulating and tissue-bound autoantibodies against keratinocyte cell surface antigens, specifically desmoglein (Dsg) 1 and 3. The pathogenic role of anti-Dsg antibodies is well-established, while the mechanism of blister formation is only partly defined. We have applied...

Università della Svizzera italiana

Quality control mechanisms of protein biogenesis : proteostasis dies hard

Bergmann, Timothy Jan ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: AIMS biophysics, 2016, vol. 3, no. 4, p. 456-478

The biosynthesis of proteins entails a complex series of chemical reactions that transform the information stored in the nucleic acid sequence into a polypeptide chain that needs to properly fold and reach its functional location in or outside the cell. It is of no surprise that errors might occur that alter the polypeptide sequence leading to a non-functional proteins or that impede delivery...

Università della Svizzera italiana

LPS nephropathy in mice is ameliorated by IL-2 independently of regulatory T cells activity

Bertelli, Roberta ; Di Donato, Armando ; Cioni, Michela ; Grassi, Fabio ; Ikehata, Masami ; Bonanni, Alice ; Rastaldi, Maria Pia ; Ghiggeri, Gian Marco

In: Plos one, 2014, vol. 9, no. 10, p. e111285

Immunosuppressive regulatory T cells (Tregs) have been hypothesized to exert a protective role in animal models of spontaneous (Buffalo/Mna) and/or drug induced (Adriamycin) nephrotic syndrome. In this study, we thought to define whether Tregs can modify the outcome of LPS nephropathy utilizing IL-2 as inducer of tissue and circulating Tregs. LPS (12 mg/Kg) was given as single shot in C57BL/6,...

Università della Svizzera italiana

Proteostasis : bad news and good news from the endoplasmic reticulum

Noack, Julia ; Brambilla Pisoni, Giorgia ; Molinari, Maurizio

In: Swiss medical weekly, 2014, vol. 144, p. w14001

The endoplasmic reticulum (ER) is an intracellular compartment dedicated to the synthesis and maturation of secretory and membrane proteins, totalling about 30% of the total eukaryotic cells proteome. The capacity to produce correctly folded polypeptides and to transport them to their correct intra- or extracellular destinations relies on proteostasis networks that regulate and balance the...

Université de Fribourg

Injured axons instruct schwann cells to build constricting actin spheres to accelerate axonal disintegration

Vaquié, Adrien ; Sauvain, Alizée ; Duman, Mert ; Nocera, Gianluigi ; Egger, Boris ; Meyenhofer, Felix ; Falquet, Laurent ; Bartesaghi, Luca ; Chrast, Roman ; Lamy, Christophe Maurice ; Bang, Seokyoung ; Lee, Seung-Ryeol ; Jeon, Noo Li ; Ruff, Sophie ; Jacob, Claire

In: Cell Reports, 2019, vol. 27, no. 11, p. 3152-3166.e7

After a peripheral nerve lesion, distal ends of injured axons disintegrate into small fragments that are subsequently cleared by Schwann cells and later by macrophages. Axonal debris clearing is an early step of the repair process that facilitates regeneration. We show here that Schwann cells promote distal cut axon disintegration for timely clearing. By combining cell-based and in vivo...

Università della Svizzera italiana

T regulatory cells are markers of disease activity in multiple sclerosis patients

Dalla Libera, Dacia ; Di Mitri, Diletta ; Bergami, Alessandra ; Centonze, Diego ; Gasperini, Claudio ; Grasso, Maria Grazia ; Galgani, Simona ; Martinelli, Vittorio ; Comi, Giancarlo ; Avolio, Carlo ; Martino, Gianvito ; Borsellino, Giovanna ; Sallusto, Federica ; Battistini,Luca ; Furlan, Roberto

In: Plos one, 2011, vol. 6, no. 6, p. e21386

FoxP3+ Treg cells are believed to play a role in the occurrence of autoimmunity and in the determination of clinical recurrences. Contradictory reports are, however, available describing frequency and function of Treg cells during autoimmune diseases. We examined, by both polychromatic flow cytometry, and real-time RT-PCR, several Treg markers in peripheral blood mononuclear cells from...