SIVA-1 regulates apoptosis and synaptic function by modulating XIAP interaction with the death receptor antagonist FAIM-L

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2020
Author
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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Coccia, Elena; Planells Ferrer, Laura; Badillos-Rodríguez, Raquel; Pascual, Marta; Segura Ginard, Miguel Francisco; Fernández-Hernández, Rita; ... Comella i Carnicé, Joan Xavier. (2020) . SIVA-1 regulates apoptosis and synaptic function by modulating XIAP interaction with the death receptor antagonist FAIM-L. Cell Death and Disease, 2020, vol. 11, núm. 2, p. 82. https://doi.org/10.1038/s41419-020-2282-x.
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Abstract
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.
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http://hdl.handle.net/10459.1/69120
DOI
https://doi.org/10.1038/s41419-020-2282-x
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Cell Death and Disease, 2020, vol. 11, núm. 2, p. 82
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cc-by, (c) Coccia et al., 2020
Except where otherwise noted, this item's license is described as cc-by, (c) Coccia et al., 2020