title: Biochemical nature of Russell Bodies.
abstract: Professional secretory cells produce and release abundant proteins. Particularly in case of mutations and/or insufficient chaperoning, these can aggregate and become toxic within or amongst cells. Immunoglobulins (Ig) are no exception. In the extracellular space, certain Ig-L chains form fibrils causing systemic amyloidosis. On the other hand, Ig variants lacking the first constant domain condense in dilated cisternae of the early secretory compartment, called Russell Bodies (RB), frequently observed in plasma cell dyscrasias, autoimmune diseases and chronic infections. RB biogenesis can be recapitulated in lymphoid and non-lymphoid cells by expressing mutant Ig-μ, providing powerful models to investigate the pathophysiology of endoplasmic reticulum storage disorders. Here we analyze the aggregation propensity and the biochemical features of the intra- and extra-cellular Ig deposits in human cells, revealing β-aggregated features for RB.
authors.affiliation: Unit of Protein Transport and Secretion, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Mossuto
authors.affiliation: 1] Department of Physics, University of Milano-Bicocca [2] Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, Milano, 20126, Italy.
authors.forename: Diletta
authors.initials: D
authors.lastname: Ami
authors.affiliation: 1] Unit of Protein Transport and Secretion, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy [2] Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Anelli
authors.affiliation: Unit of Protein Transport and Secretion, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Fagioli
authors.affiliation: 1] Department of Physics, University of Milano-Bicocca [2] Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, Milano, 20126, Italy.
authors.forename: Silvia Maria
authors.initials: SM
authors.lastname: Doglia
authors.affiliation: 1] Unit of Protein Transport and Secretion, Division of Genetics and Cell Biology, IRCCS San Raffaele Scientific Institute, Milan, Italy [2] Vita-Salute San Raffaele University, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
mesh_terms: D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D007148:Immunoglobulin mu-Chains / Q000235:genetics / Q000378:metabolism*; D018613:Microscopy, Confocal; D009154:Mutation; D013055:Spectrophotometry, Infrared
chemical_list: D007148:Immunoglobulin mu-Chains