V-014 | The Physiological Relevance of Nedp1: Insights from Different Animal Models

Cellular and Molecular Neurobiology
Author: Ivana Marcela Linenberg | Email: ivanamlinen@gmail.com

Ivana M Linenberg^1°, Sebastian A Giusti^1°,Mariana Erdocia^1°, Luciana F Godoy^2°, Diego M Jofré^2°, Daniel Hochbaum^2°, Damian Refojo^1°

^1° IBioBA-CONICET-MPSP
^2° CEBBAD-UMAI

Nedd8 belongs to the Ubiquitin-like protein family. Like Ubiquitin, Nedd8 covalently binds to its target proteins through a conjugation cascade through specific enzymes, a process called neddylation. Neddylation is reversible and is mediated by two deneddlyases: the signalosome COP9, which deconjugates Nedd8 from Cullins, the most studied neddylation target, and Nedp1, the main protease responsible for removing Nedd8 from all the other proteins. The biological relevance of Nedp1, and non-Cullin neddylation by extension, has been historically questioned.
To address this, we studied the physiological relevance of Nedp1 in various biological models. Using transgenic invertebrate models, we demonstrate that the loss of function of Nedp1 orthologue negatively affects fertility and survival in D. melanogaster and that Nedp1 confers resistance to both D. melanogaster and C. elegans upon stress conditions.
We show for the first time that Nedp1 is essential in a murine model, indicating its biological relevance is greater in mammals. Moreover, Nedp1 deletion in neural tube-derived cells leads to morphological alterations in the mouse brain. These results contribute to understanding the physiological relevance of neddylation in general and of Nedp1, in particular, across diverse contexts and models.