• Visit the USI website
  • Go back to the homepage

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

Revealing Mechanisms Regulating Recovery from Transient ER Stress in Mammalian Cells

Research area: Protein Folding and Quality Control

Group leaders: Maurizio Molinari


Status: In progress

Eukaryotic cells respond to changes in ER homeostasis by reducing the synthesis of cargo proteins, by inducing transcription/translation of ER-resident gene products and by expanding the ER volume in a series of events collectively named the UPR. The temporary reduction in cargo protein synthesis coupled with the enhanced luminal content of molecular chaperones, folding and ERAD factors should reduce the burden of unfolded and misfolded polypeptides in the ER lumen and re-establish proteostasis (i.e., the capacity to produce the functional cellular proteome in appropriate amount). Most studies have focused on transcriptional events and their regulation during UPR elicited by drugs that dramatically impair cellular (and not only ER) homeostasis by compromising the regulation of redox conditions, calcium concentration or protein glycosylation.

The aim of this project is to establish experimental conditions resulting in triggering reversible ER stresses. To this end, cells will be transiently challenged with different drugs perturbing compartmental homeostasis. Alternatively, cell lines will be generated, which are characterized by inducible, tetracycline-controlled expression of a collection of folding-defective polypeptides. The model proteins will be individually expressed at levels triggering an UPR and their synthesis will then be stopped upon tetracycline wash out. How do cells return to the “steady state situation” (i.e. how the excess chaperones produced during the stress phase is cleared from cells during the “recovery phase” occurring after ER stress resolution is the main subject of our study.



SEC62 accumulates in autophagic vacuoles upon lysosomal inhibition during stress recovery. Mouse embryonic fibroblasts transfected or not with GFP-LC3 (upper panels) or GFP-RAB7 (middle panels) were treated with 50 nM BafA1 during 12 h of stress recovery. Immunostains are with anti-SEC62 (all panels) and anti-LAMP1 (lower panels).