Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation
- Institut Pasteur, France
- Institut Pasteur, France
Abstract
Disruption of the sumoylation/desumoylation equilibrium is associated with several disease states such as cancer and infections, however the mechanisms regulating the global SUMO balance remain poorly defined. Here, we show that infection by Shigella flexneri, the causative agent of human bacillary dysentery, switches off host sumoylation during epithelial cell infection in vitro and in vivo and that this effect is mainly mediated by a calcium/calpain-induced cleavage of the SUMO E1 enzyme SAE2, thus leading to sumoylation inhibition. Furthermore, we describe a mechanism by which Shigella promotes its own invasion by altering the sumoylation state of RhoGDIa, a master negative regulator of RhoGTPase activity and actin polymerization. Together, our data suggest that SUMO modification is essential to restrain pathogenic bacterial entry by limiting cytoskeletal rearrangement induced by bacterial effectors. Moreover, these findings identify calcium-activated calpains as powerful modulators of cellular sumoylation levels with potentially broad implications in several physiological and pathological situations.
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Author details
Funding
Ligue Contre le Cancer (Post-doc fellowship to P. Lapaquette and labelled team to A. Dejean)
- Pierre Lapaquette
- Anne Dejean
Institut Pasteur
- Philippe Sansonetti
- Anne Dejean
Institut National Du Cancer
- Anne Dejean
European Research Council (SUMOSTRESS)
- Anne Dejean
Sidaction
- Sabrina Fritah
Odyssey RE
- Anne Dejean
Institut National de la Santé et de la Recherche Médicale
- Philippe Sansonetti
- Anne Dejean
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: Animal experiments were performed accordingly to the guidelines of the Institut Pasteur's ethical committee for animal use in research (CETEA number 2013-0028).
Copyright
© 2017, Lapaquette et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation
eLife 6:e27444.
https://doi.org/10.7554/eLife.27444
