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Institute for Research in Biomedicine
Istituto di Ricerca in Biomedicina

Via Vincenzo Vela 6 - CH-6500 Bellinzona
Tel. +41 91 820 0300 - Fax +41 91 820 0302 - info [at] irb [dot] usi [dot] ch

Protein Folding and Quality Control

Maurizio Molinari, Group Leader

Timothy Jan Bergmann, Elisa Fasana, Ilaria Fregno, Carmela Galli Molinari, Concetta Guerra, Marika Kucińska, Tatiana Soldà

The endoplasmic reticulum (ER) contains high concentrations of molecular chaperones and enzymes that assist maturation of newly synthesized polypeptides destined to the extracellular space, the plasma membrane and the organelles of the endocytic and secretory pathways. It also contains quality control factors that select folding-defective proteins for ER retention and/or ER-associated degradation (ERAD). Mutations, deletions and truncations in the polypeptide sequences may cause protein-misfolding diseases characterized by a “loss-of-function” upon degradation of the mutant protein or by a “gain-of-toxic-function” upon its aggregation/deposition. Pathogens hijack the machineries regulating protein biogenesis, quality control and transport for host invasion, genome replication and progeny production. Our long-standing interest is to understand the molecular mechanisms regulating chaperone-assisted protein folding and the quality control processes determining whether a polypeptide can be secreted, should be retained in the ER, or should be selected for degradation. More recently, particular emphasis has been given to the characterization of transcriptional and post translational responses activated by cells experiencing ER stresses, to the mechanisms ensuring clearance of polymeric and aggregated proteins from the ER and to the study of select rare diseases such as α1-antitrypsin deficiency, lysosomal storage diseases and Charcot-Marie-Tooth 1B neuropathy. A thorough knowledge of the processes ensuring protein biogenesis and maintenance of cellular proteostasis will be instrumental to identify drug targets and/or to design therapies for diseases caused by inefficient functioning of the cellular protein factory, resulting from expression of defective gene products (e.g. rare genetic disorders), or elicited by pathogens.

Così i “rifiuti” delle cellule possono innescare malattie