title: Lamin A/C mutants disturb sumo1 localization and sumoylation in vitro and in vivo.
abstract: A-type lamins A and C are nuclear intermediate filament proteins in which mutations have been implicated in multiple disease phenotypes commonly known as laminopathies. A few studies have implicated sumoylation in the regulation of A-type lamins. Sumoylation is a post-translational protein modification that regulates a wide range of cellular processes through the attachment of small ubiquitin-related modifier (sumo) to various substrates. Here we showed that laminopathy mutants result in the mislocalization of sumo1 both in vitro (C2C12 cells overexpressing mutant lamins A and C) and in vivo (primary myoblasts and myopathic muscle tissue from the Lmna(H222P/H222P) mouse model). In C2C12 cells, we showed that the trapping of sumo1 in p.Asp192Gly, p.Gln353Lys, and p.Arg386Lys aggregates of lamin A/C correlated with an increased steady-state level of sumoylation. However, lamin A and C did not appear to be modified by sumo1. Our results suggest that mutant lamin A/C alters the dynamics of sumo1 and thus misregulation of sumoylation may be contributing to disease progression in laminopathies.
authors.affiliation: Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Émilie
authors.initials: É
authors.lastname: Boudreau
authors.forename: Sarah
authors.initials: S
authors.lastname: Labib
authors.forename: Anne T
authors.initials: AT
authors.lastname: Bertrand
authors.forename: Valérie
authors.initials: V
authors.lastname: Decostre
authors.forename: Pierrette M
authors.initials: PM
authors.lastname: Bolongo
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sylvius
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Frédérique
authors.initials: F
authors.lastname: Tesson
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015870:Gene Expression; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D009135:Muscular Diseases / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D032448:Myoblasts, Skeletal / Q000378:metabolism; D061251:Primary Cell Culture; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D025842:SUMO-1 Protein / Q000378:metabolism*; D058207:Sumoylation; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9
chemical_list: D034904:Lamin Type A; D020033:Protein Isoforms; D025842:SUMO-1 Protein; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9