Lamin A/C Mutants Disturb Sumo1 Localization and Sumoylation in Vitro and in Vivo

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Title: Lamin A/C Mutants Disturb Sumo1 Localization and Sumoylation in Vitro and in Vivo
Authors: Boudreau, Émilie
Labib, Sarah
Bertrand, Anne T.
Decostre, Valérie
Bolongo, Pierrette M.
Sylvius, Nicolas
Bonne, Gisèle
Tesson, Frédérique
Date: 2012
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 LmnaH222P/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.
URL: http://hdl.handle.net/10393/23909
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0045918
DOI: 10.1371/journal.pone.0045918
CollectionLibre accès uOttawa - Publications // uOttawa Open Access - Publications
Sciences de la santé // Health Sciences
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