Lamin A/C Mutants Disturb Sumo1 Localization and Sumoylation in Vitro and in Vivo
|
| |
| Authors: | émilie Boudreau Sarah Labib Anne T Bertrand Valérie Decostre Pierrette M Bolongo Nicolas Sylvius Gisèle Bonne Frédérique Tesson |
| |
| Institution: | 1. Interdisciplinary School of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada.; 2. UMRS 974, Inserm, Paris, France.; 3. Université Pierre et Marie Curie-Paris Institut de Myologie, Paris, France.; 4. Service de Biochimie Métabolique, U.F. Cardiogénétique et Myogénétique, AP-HP Groupe Hospitalier Pitié-Salpêtrière, Paris, France.; “Mario Negri” Institute for Pharmacological Research, Italy, |
| |
| 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. |
| |
| Keywords: | |
|
|
