title: SEL1L and HRD1 are involved in the degradation of unassembled secretory Ig-mu chains.
abstract: When expressed in the absence of light chains, secretory Ig-micro chains (micro(s)) undergo endoplasmic reticulum associated degradation (ERAD). This process involves the recognition of terminally misfolded or unassembled molecules, their retro-translocation across the ER membrane and ubiquitination for degradation by cytosolic proteasomes. The molecular components of the ERAD pathway and their coordination remain largely unknown. Here we employed co-immunoprecipitation, silencing or over-expression assays to show that SEL1L and HRD1 are involved in the degradation of unassembled Ig-micro(s), but have minor effects on another substrate, TCR-alpha. SEL1L and HRD1 localize in the early secretory apparatus and are induced by ER stress and during B cell differentiation, concomitantly with the onset of massive IgM secretion. These findings reveal a role for SEL1L and HRD1 in IgM quality control.
authors.affiliation: Institute for Biomedical Technologies, National Research Council, Segrate, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Mieko
authors.initials: M
authors.lastname: Otsu
authors.forename: Claudio
authors.initials: C
authors.lastname: Fagioli
authors.forename: Simone
authors.initials: S
authors.lastname: Martino
authors.forename: Lavinia Vittoria
authors.initials: LV
authors.lastname: Lotti
authors.forename: Roberto
authors.initials: R
authors.lastname: Sitia
authors.forename: Ida
authors.initials: I
authors.lastname: Biunno
mesh_terms: D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D006801:Humans; D007075:Immunoglobulin M / Q000378:metabolism*; D047468:Immunoprecipitation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007075:Immunoglobulin M; D011506:Proteins; D012333:RNA, Messenger; D016693:Receptors, Antigen, T-Cell, alpha-beta; C117384:SEL1L protein, human; C033027:secretory IgM; C482345:SYVN1 protein, human; D044767:Ubiquitin-Protein Ligases