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Títol:
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SIVA-1 regulates apoptosis and synaptic function by modulating XIAP interaction with the death receptor antagonist FAIM-L
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Autor/a:
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Coccia, Elena; Planells Ferrer, Laura; Badillos-Rodríguez, Raquel; Pascual, Marta; Segura Ginard, Miguel Francisco; Fernández-Hernández, Rita; López-Soriano, Joaquín; Garí Marsol, Eloi; Soriano, Eduardo; Barneda-Zahonero, Bruna; Moubarak, Rana S.; Pérez-García, M. Jose; Comella i Carnicé, Joan Xavier
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Notes:
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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.
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). |
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Matèries:
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-Apoptosi
-Neurones |
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Drets:
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cc-by, (c) Coccia et al., 2020
http://creativecommons.org/licenses/by/4.0/
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Tipus de document:
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Article
Article - Versió publicada |
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Publicat per:
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Springer Nature
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Compartir:
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