TY - JOUR
T1 - Shigella entry unveils a calcium/calpain-dependent mechanism for inhibiting sumoylation
AU - Lapaquette, Pierre
AU - Fritah, Sabrina
AU - Lhocine, Nouara
AU - Andrieux, Alexandra
AU - Nigro, Giulia
AU - Mounier, Joëlle
AU - Sansonetti, Philippe
AU - Dejean, Anne
N1 - Funding Information:
We acknowledge Chuanshu Huang and Mark R Philips for the generous gifts of RhoGDIa plasmids. We thank Peter A Greer for providing the Capns1 WT and Capns1 KO MEFs. We are grateful to Jacob S Seeler for providing unpublished auxin-inducible degron-UBC9 HT1080 cells and for intellectual input. We also thank Sandrine Etienne-Manneville for helpful discussions. This work was supported by grants from LNCC (Equipe labellisée), Odyssey-RE, INCa and ERC-AdG ’SUMOSTRESS’. PL was supported by LNCC. SF was supported by EEC ’RUBICON’ and Sidaction.
Funding Information:
We acknowledge Chuanshu Huang and Mark R Philips for the generous gifts of RhoGDIa plasmids. We thank Peter A Greer for providing the Capns1 WT and Capns1 KO MEFs. We are grateful to Jacob S Seeler for providing unpublished auxin-inducible degron-UBC9 HT1080 cells and for intel- lectual input. We also thank Sandrine Etienne-Manneville for helpful discussions. This work was sup- ported by grants from LNCC (Equipe labellise´ e), Odyssey-RE, INCa and ERC-AdG ’SUMOSTRESS’. PL was supported by LNCC. SF was supported by EEC ’RUBICON’ and Sidaction Ligue Contre le Cancer Post-doc fellowship Pierre Lapaquette Sidaction Sabrina Fritah Institut Pasteur Philippe Sansonetti Anne Dejean Institut National de la Santé et de la Recherche Mé dicale Philippe Sansonetti Anne Dejean Institut National Du Cancer Anne Dejean European Research Council SUMOSTRESS Anne Dejean Odyssey RE Anne Dejean Ligue Contre le Cancer Labelled team Anne Dejean.
Publisher Copyright:
© Lapaquette et al.
PY - 2017/12/12
Y1 - 2017/12/12
N2 - 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 RhoGDIα, 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.
AB - 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 RhoGDIα, 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.
UR - http://www.scopus.com/inward/record.url?scp=85040925191&partnerID=8YFLogxK
U2 - 10.7554/eLife.27444.001
DO - 10.7554/eLife.27444.001
M3 - Article
C2 - 29231810
AN - SCOPUS:85040925191
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e27444
ER -