dc.contributor.author |
Coccia, Elena |
dc.contributor.author |
Planells Ferrer, Laura |
dc.contributor.author |
Badillos-Rodríguez, Raquel |
dc.contributor.author |
Pascual, Marta |
dc.contributor.author |
Segura Ginard, Miguel Francisco |
dc.contributor.author |
Fernández-Hernández, Rita |
dc.contributor.author |
López-Soriano, Joaquín |
dc.contributor.author |
Garí Marsol, Eloi |
dc.contributor.author |
Soriano, Eduardo |
dc.contributor.author |
Barneda-Zahonero, Bruna |
dc.contributor.author |
Moubarak, Rana S. |
dc.contributor.author |
Pérez-García, M. Jose |
dc.contributor.author |
Comella i Carnicé, Joan Xavier |
dc.date |
2020-06-23T11:16:09Z |
dc.date |
2020-06-23T11:16:09Z |
dc.date |
2020 |
dc.identifier |
2041-4889 |
dc.identifier |
http://hdl.handle.net/10459.1/69120 |
dc.identifier |
https://doi.org/10.1038/s41419-020-2282-x |
dc.identifier.uri |
http://hdl.handle.net/10459.1/69120 |
dc.description |
The long isoform of Fas apoptosis inhibitory molecule (FAIM-L) is a neuron-specific death receptor antagonist that modulates apoptotic cell death and mechanisms of neuronal plasticity. FAIM-L exerts its antiapoptotic action by binding to X-linked inhibitor of apoptosis protein (XIAP), an inhibitor of caspases, which are the main effectors of apoptosis. XIAP levels are regulated by the ubiquitin-proteasome pathway. FAIM-L interaction with XIAP prevents the ubiquitination and degradation of the latter, thereby allowing it to inhibit caspase activation. This interaction also modulates non-apoptotic functions of caspases, such as the endocytosis of AMPA receptor (AMPAR) in hippocampal long-term depression (LTD). The molecular mechanism of action exerted by FAIM-L is unclear since the consensus binding motifs are still unknown. Here, we performed a two-hybrid screening to discover novel FAIM-L-interacting proteins. We found a functional interaction of SIVA-1 with FAIM-L. SIVA-1 is a proapoptotic protein that has the capacity to interact with XIAP. We describe how SIVA-1 regulates FAIM-L function by disrupting the interaction of FAIM-L with XIAP, thereby promoting XIAP ubiquitination, caspase-3 activation and neuronal death. Furthermore, we report that SIVA-1 plays a role in receptor internalization in synapses. SIVA-1 is upregulated upon chemical LTD induction, and it modulates AMPAR internalization via non-apoptotic activation of caspases. In summary, our findings uncover SIVA-1 as new functional partner of FAIM-L and demonstrate its role as a regulator of caspase activity in synaptic function. |
dc.description |
This work was funded by grants awarded by the Spanish “Ministerio de Economía y Competitividad” (SAF2013-47989-R, SAF2016-80236-R, CIBERNED CB06/05/1104 and PIE13/00027), the Generalitat de Catalunya (2014SGR1609), and the Fundació La Marató de TV3 (201414-30) to J.X.C. E.C. is supported by a predoctoral fellowship from the Vall d´Hebron Research Institute (VHIR). R.B. is supported by a predoctoral fellowship from the Spanish “Ministerio de Economía y Competitividad” (BES-2018-080846). |
dc.language |
eng |
dc.publisher |
Springer Nature |
dc.relation |
MINECO/PN2013-2016/SAF2013-47989-R |
dc.relation |
Reproducció del document publicat a https://doi.org/10.1038/s41419-020-2282-x |
dc.relation |
Cell Death and Disease, 2020, vol. 11, núm. 2, p. 82 |
dc.relation |
MINECO/PN2013-2016/SAF2016-80236-R |
dc.rights |
cc-by, (c) Coccia et al., 2020 |
dc.rights |
http://creativecommons.org/licenses/by/4.0/ |
dc.rights |
info:eu-repo/semantics/openAccess |
dc.subject |
Apoptosi |
dc.subject |
Neurones |
dc.title |
SIVA-1 regulates apoptosis and synaptic function by modulating XIAP interaction with the death receptor antagonist FAIM-L |
dc.type |
info:eu-repo/semantics/article |
dc.type |
info:eu-repo/semantics/publishedVersion |