Publications
2020 |
Chernorudskiy, A; Varone, E; Colombo, S F; Fumagalli, S; Cagnotto, A; Cattaneo, A; Briens, M; Baltzinger, M; Kuhn, L; Bachi, A; Berardi, A; Salmona, M; Musco, G; Borgese, N; Lescure, A; Zito, E Selenoprotein N is an endoplasmic reticulum calcium sensor that links luminal calcium levels to a redox activity Article de journal Proc Natl Acad Sci U S A, 117 (35), p. 21288-21298, 2020, ISBN: 32817544. Résumé | Liens | BibTeX | Étiquettes: LESCURE, LESCURE calcium sensor SEPN1 endoplasmic reticulum stress of the endoplasmic reticulum, Unité ARN @article{, title = {Selenoprotein N is an endoplasmic reticulum calcium sensor that links luminal calcium levels to a redox activity}, author = {A Chernorudskiy and E Varone and S F Colombo and S Fumagalli and A Cagnotto and A Cattaneo and M Briens and M Baltzinger and L Kuhn and A Bachi and A Berardi and M Salmona and G Musco and N Borgese and A Lescure and E Zito}, url = {https://pubmed.ncbi.nlm.nih.gov/32817544/}, doi = {10.1073/pnas.2003847117}, isbn = {32817544}, year = {2020}, date = {2020-01-01}, journal = {Proc Natl Acad Sci U S A}, volume = {117}, number = {35}, pages = {21288-21298}, abstract = {The endoplasmic reticulum (ER) is the reservoir for calcium in cells. Luminal calcium levels are determined by calcium-sensing proteins that trigger calcium dynamics in response to calcium fluctuations. Here we report that Selenoprotein N (SEPN1) is a type II transmembrane protein that senses ER calcium fluctuations by binding this ion through a luminal EF-hand domain. In vitro and in vivo experiments show that via this domain, SEPN1 responds to diminished luminal calcium levels, dynamically changing its oligomeric state and enhancing its redox-dependent interaction with cellular partners, including the ER calcium pump sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). Importantly, single amino acid substitutions in the EF-hand domain of SEPN1 identified as clinical variations are shown to impair its calcium-binding and calcium-dependent structural changes, suggesting a key role of the EF-hand domain in SEPN1 function. In conclusion, SEPN1 is a ER calcium sensor that responds to luminal calcium depletion, changing its oligomeric state and acting as a reductase to refill ER calcium stores.}, keywords = {LESCURE, LESCURE calcium sensor SEPN1 endoplasmic reticulum stress of the endoplasmic reticulum, Unité ARN}, pubstate = {published}, tppubtype = {article} } The endoplasmic reticulum (ER) is the reservoir for calcium in cells. Luminal calcium levels are determined by calcium-sensing proteins that trigger calcium dynamics in response to calcium fluctuations. Here we report that Selenoprotein N (SEPN1) is a type II transmembrane protein that senses ER calcium fluctuations by binding this ion through a luminal EF-hand domain. In vitro and in vivo experiments show that via this domain, SEPN1 responds to diminished luminal calcium levels, dynamically changing its oligomeric state and enhancing its redox-dependent interaction with cellular partners, including the ER calcium pump sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). Importantly, single amino acid substitutions in the EF-hand domain of SEPN1 identified as clinical variations are shown to impair its calcium-binding and calcium-dependent structural changes, suggesting a key role of the EF-hand domain in SEPN1 function. In conclusion, SEPN1 is a ER calcium sensor that responds to luminal calcium depletion, changing its oligomeric state and acting as a reductase to refill ER calcium stores. |