Università della Svizzera italiana

Endoplasmic reticulum and lysosomal quality control of four nonsense mutants of iduronate 2-sulfatase linked to Hunter’s syndrome

Marazza, Alessandro ; Galli, Carmela ; Fasana, Elisa ; Sgrignani, Jacopo ; Burda, Patricie ; Enrico M. A. Fassi ; Matthias Baumgartner ; Andrea Cavalli ; Maurizio Molinari

In: DNA and cell biology

Hunter’s syndrome (mucopolysaccharidosis type II) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate 2-sulfatase (IDS) gene. Motivated by the case of a child affected by this syndrome, we compared the intracellular fate of wild type IDS (IDSWT) and of four nonsense mutations of IDS (IDSL482X, IDSY452X, IDSR443X and IDSW337X) generating progressively shorter ...

Università della Svizzera italiana

Chronic delivery of antibody fragments using immunoisolated cell implants as a passive vaccination tool

Belaunzaran, Osiris Marroquin ; Cordero, Maria Isabel ; Setola, Veronica ; Bianchi, Siro ; Galli, Carmela ; Bouche, Nicolas ; Mlynarik, Vladimir ; Gruetter, Rolf ; Sandi, Carmen ; Bensadoun, Jean-Charles ; Molinari, Maurizio ; Aebischer, Patrick

In: Plos one, 2011, vol. 6, no. 4, p. e18268

Background: Monoclonal antibodies and antibody fragments are powerful biotherapeutics for various debilitating diseases. However, high production costs, functional limitations such as inadequate pharmacokinetics and tissue accessibility are the current principal disadvantages for broadening their use in clinic. Methodology and Principal Findings: We report a novel method for the long-term ...

Università della Svizzera italiana

Malectin participates in a backup glycoprotein quality control pathway in the mammalian ER

Galli, Carmela ; Bernasconi, Riccardo ; Soldà, Tatiana ; Calanca, Verena ; Molinari, Maurizio

In: Plos one, 2011, vol. 6, no. 1, p. e16304

Malectin is a conserved, endoplasmic reticulum (ER)-resident lectin that recognizes high mannose oligosaccharides displaying terminal glucose residues. Here we show that Malectin is an ER stress-induced protein that selectively associates with glycopolypeptides without affecting their entry and their retention in the Calnexin chaperone system. Analysis of the obligate Calnexin client...

Università della Svizzera italiana

Cyclosporine A-sensitive, cyclophilin B-dependent endoplasmic reticulum-associated degradation

Bernasconi, Riccardo ; Soldà, Tatiana ; Galli, Carmela ; Pertel, Thomas ; Luban, Jeremy ; Molinari, Maurizio

In: Plos one, 2010, vol. 5, no. 9, p. e13008

Peptidyl-prolyl cis/trans isomerases (PPIs) catalyze cis/trans isomerization of peptide bonds preceding proline residues. The involvement of PPI family members in protein refolding has been established in test tube experiments. Surprisingly, however, no data is available on the involvement of endoplasmic reticulum (ER)-resident members of the PPI family in protein folding, quality control or...

Università della Svizzera italiana

Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-LS substrates

Bernasconi, Riccardo ; Galli, Carmela ; Calanca, Verena ; Nakajima, Toshihiro ; Molinari, Maurizio

In: The journal of cell biology, 2010, vol. 188, no. 2, p. 223–235

Sophisticated quality control mechanisms prolong retention of protein-folding intermediates in the endoplasmic reticulum (ER) until maturation while sorting out terminally misfolded polypeptides for ER-associated degradation (ERAD). The presence of structural lesions in the luminal, transmembrane, or cytosolic domains determines the classification of misfolded polypeptides as ERAD-L, -M, or -C...