protein folding; folding enzymes; endoplasmic reticulum; Unfolded protein responses; N-linked oligosaccharides; protein quality control; molecular chaperones; protein degradation
Forrester Alison, De Leonibus Chiara, Grumati Paolo, Fasana Elisa, Piemontese Marilina, Staiano Leopoldo, Fregno Ilaria, Raimondi Andrea, Marazza Alessandro, Bruno Gemma, Iavazzo Maria, Intartaglia Daniela, Seczynska Marta, van Anken Eelco, Conte Ivan, De Matteis Maria Antonietta, Dikic Ivan, Molinari Maurizio, Settembre Carmine (2018), A selective ER‐phagy exerts procollagen quality control via a Calnexin‐FAM134B complex, in The EMBO Journal
Bergmann Timothy J., Molinari Maurizio (2018), Three branches to rule them all? UPR signalling in response to chemically versus misfolded proteins-induced ER stress, in Biology of the Cell
, 110(9), 197-204.
Fregno Ilaria, Fasana Elisa, Bergmann Timothy J, Raimondi Andrea, Loi Marisa, Soldà Tatiana, Galli Carmela, D'Antuono Rocco, Morone Diego, Danieli Alberto, Paganetti Paolo, van Anken Eelco, Molinari Maurizio (2018), ER‐to‐lysosome‐associated degradation of proteasome‐resistant ATZ polymers occurs via receptor‐mediated vesicular transport, in The EMBO Journal
, 37(17), e99259-e99259.
Guerra Concetta, Brambilla Pisoni Giorgia, Soldà Tatiana, Molinari Maurizio (2018), The reductase TMX1 contributes to ERAD by preferentially acting on membrane-associated folding-defective polypeptides, in Biochemical and Biophysical Research Communications
, 503(2), 938-943.
Loi Marisa, Fregno Ilaria, Guerra Concetta, Molinari Maurizio (2018), Eat it right: ER-phagy and recovER-phagy, in Biochemical Society Transactions
, 46(3), 699-706.
Bergmann Timothy J., Fregno Ilaria, Fumagalli Fiorenza, Rinaldi Andrea, Bertoni Francesco, Boersema Paul J., Picotti Paola, Molinari Maurizio (2018), Chemical stresses fail to mimic the unfolded protein response resulting from luminal load with unfolded polypeptides, in Journal of Biological Chemistry
, 293(15), 5600-5612.
Fregno Ilaria, Molinari Maurizio (2018), Endoplasmic reticulum turnover: ER-phagy and other flavors in selective and non-selective ER clearance, in F1000Research
, 7, 454-454.
Fregno I., Molinari M. (2018), A J-Protein Co-chaperone Recruits BiP to Monomerize IRE1 and Repress the Unfolded Protein Response, in F1000Prime
Fregno I., Molinari M. (2017), A method for the acute and rapid degradation of endogenous proteins, in F1000Prime
Fregno I., Molinari M. (2017), Cell-wide analysis of protein thermal unfolding reveals determinants of thermostability, in F1000Prime
Fregno I., Molinari M. (2017), Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy, in F1000Prime
Fregno I., Molinari M. (2017), Molecular mechanism of substrate processing by the cdc48 atpase complex, in F1000Prime
Fregno I., Molinari M. (2017), Polyglutamine tracts regulate beclin 1-dependent autophagy, in F1000Prime
Fregno I., Molinari M. (2017), Reticulon 3-dependent ER-PM contact sites control EGFR nonclathrin endocytosis, in F1000Prime
Fregno I., Molinari M. (2017), Reversible protein aggregation is a protective mechanism to ensure cell cycle restart after stress, in F1000Prime
Fregno I., Molinari M. (2017), STING Senses Microbial Viability to Orchestrate Stress-Mediated Autophagy of the Endoplasmic Reticulum, in F1000Prime
Bergmann Timothy J., Fumagalli Fiorenza, Loi Marisa, Molinari Maurizio (2016), Role of SEC62 in ER maintenance: A link with ER stress tolerance in SEC62-overexpressing tumors?, in Molecular & Cellular Oncology
, (2), e1264351-e1264351.
Fumagalli Fiorenza, Noack Julia, Bergmann Timothy J., Cebollero Eduardo, Pisoni Giorgia Brambilla, Fasana Elisa, Fregno Ilaria, Galli Carmela, Loi Marisa, Soldà Tatiana, D’Antuono Rocco, Raimondi Andrea, Jung Martin, Melnyk Armin, Schorr Stefan, Schreiber Anne, Simonelli Luca, Varani Luca, Wilson-Zbinden Caroline, Zerbe Oliver, Hofmann Kay, Peter Matthias, Quadroni Manfredo, Zimmermann Richard, et al. (2016), Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery, in Nature Cell Biology
, (11), 1173-1184.
Brambilla Pisoni Giorgia, Molinari Maurizio (2016), Five Questions (with their Answers) on ER-Associated DegradationEndoplasmic Reticulum-Associated Degradation, in Traffic
, 17(4), 341-350.
Klionsky Daniel J, Abdelmohsen Kotb, Abe Akihisa, Abedin Md Joynal, Abeliovich Hagai, Acevedo Arozena Abraham, Adachi Hiroaki, Adams Christopher M, Adams Peter D, Adeli Khosrow, Adhihetty Peter J, Adler Sharon G, Agam Galila, Agarwal Rajesh, Aghi Manish K, Agnello Maria, Agostinis Patrizia, Aguilar Patricia V, Aguirre-Ghiso Julio, Airoldi Edoardo M, Ait-Si-Ali Slimane, Akematsu Takahiko, Akporiaye Emmanuel T, Al-Rubeai Mohamed, et al. (2016), Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition), in Autophagy
, 12(1), 1-222.
Fregno Ilaria, Molinari Molinari (2016), Post ER quality control: a role for UDP-glucose:glycoprotein glucosyl transferase and p97, in Journal of Clinical Research on Rare Diseases
Secretory, membrane-bound and organelle proteins (i.e., about 30% of the eukaryotic cell proteome) are co- or post-translationally translocated into the endoplasmic reticulum (ER). ER-resident molecular chaperones, folding, quality control and degradation factors insure maintenance of cell, tissue and organism proteostasis by catalyzing rate-limiting reactions of protein folding programs, by inspecting the final shape of newly synthesized polypeptides, by selecting for degradation terminally misfolded proteins and by allowing transport at the site of activity of native, fully assembled and functional ones.The aim of the research performed in our group is to understand how mammalian cells insure expression of the cellular proteome and how they respond to variations in ER homeostasis and in ER load with folding-defective or folding-competent polypeptides.To address these questions, we have generated plasmids and cell lines for transient, stable, inducible and tunable expression of a collection of model polypeptides. Their different topology, folding-capacity, aggregation proneness, structural features, expression levels lead to engagement of specific folding, quality control, degradation and cell adaptation pathways to be characterized in molecular details in our lab. We are in the best position to study the known pathways operating to maintain cellular proteostasis, i.e., the appropriate quality and quantity of the proteome, and to characterize new ones. The ongoing collaborations with Francesco Bertoni (Institute of Oncology Research, Bellinzona, transcriptomic), Paola Picotti (ETH-Zurich, proteomic) and Manfredo Quadroni (UNI-Lausanne, interactomic) are thought to give essential contributions to our research as detailed in the Research Plan. The results of our studies may eventually lead to the development of strategies to manipulate protein folding, quality control and degradation events. Also sought-after is the capacity to intervene to modulate cell responses to expression of mutant gene products with specific structural defects thereby contrasting progression or even cure proteopathies caused by inefficient functioning of the cellular protein factory. A better comprehension of the cellular protein factory will also improve our capacity to produce high amounts of active recombinant proteins to be employed in the clinics and in the industry.