title: PaCS is a novel cytoplasmic structure containing functional proteasome and inducible by cytokines/trophic factors.
abstract: A variety of ubiquitinated protein-containing cytoplasmic structures has been reported, from aggresomes to aggresome-like induced structures/sequestosomes or particle-rich cytoplasmic structures (PaCSs) that we recently observed in some human diseases. Nevertheless, the morphological and cytochemical patterns of the different structures remain largely unknown thus jeopardizing their univocal identification. Here, we show that PaCSs resulted from proteasome and polyubiquitinated protein accumulation into well-demarcated, membrane-free, cytoskeleton-poor areas enriched in glycogen and glycosaminoglycans. A major requirement for PaCS detection by either electron or confocal microscopy was the addition of osmium to aldehyde fixatives. However, by analyzing living cells, we found that proteasome chymotrypsin-like activity concentrated in well-defined cytoplasmic structures identified as PaCSs by ultrastructural morphology and immunocytochemistry of the same cells. PaCSs differed ultrastructurally and cytochemically from sequestosomes which may coexist with PaCSs. In human dendritic or natural killer cells, PaCSs were induced in vitro by cytokines/trophic factors during differentiation/activation from blood progenitors. Our results provide evidence that PaCS is indeed a novel distinctive cytoplasmic structure which may play a critical role in the ubiquitin-proteasome system response to immune, infectious or proneoplastic stimuli.
authors.affiliation: Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Pathologic Anatomy Service, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sommi
authors.affiliation: Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Centro Grandi Strumenti, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Necchi
authors.affiliation: Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Agostina
authors.initials: A
authors.lastname: Vitali
authors.affiliation: Pediatric Hematology/Oncology Service, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Montagna
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Ada
authors.initials: A
authors.lastname: De Luigi
authors.affiliation: IRCCS Istituto di Ricerche Farmacologiche "Mario Negri", Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Salmona
authors.affiliation: Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Vittorio
authors.initials: V
authors.lastname: Ricci
authors.affiliation: Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy ; Pathologic Anatomy Service, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Solcia
mesh_terms: D000818:Animals; D019556:COS Cells; D018938:Caco-2 Cells; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000494:pharmacology*; D022083:Cytoplasmic Structures / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D019169:Jurkat Cells; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins; D046988:Proteasome Endopeptidase Complex