Neuralized family member NEURL1 is a ubiquitin ligase for the cGMP-specific phosphodiesterase 9A.

Neuralized functions as a positive regulator of the Notch pathway by promoting ubiquitination of Notch ligands via its E3 ligase activity, resulting in their efficient endocytosis and signaling. Using a yeast two-hybrid screen, we have identified a cGMP-hydrolysing phosphodiesterase, PDE9A, as a novel interactor and substrate of Neuralized E3 ubiquitin protein ligase 1 (NEURL1). We confirmed this interaction with co-immunoprecipitation experiments and show that both Neuralized Homology Repeat domains of NEURL1 can interact with PDE9A.

Rat NEURL1 3'UTR is alternatively spliced and targets mRNA to dendrites.

Neuralized, an E3 ubiquitin ligase, interacts with and positively modulates the Notch pathway by promoting ubiquitination and subsequent endocytosis of its ligands. NEURL1 mRNA is dendritically localised in the dentate gyrus of an adult rat brain, implying that it may be locally translated, but its transport mechanisms remain unstudied. Here, we report the presence of a previously unknown, shorter splice-variant of rat NEURL1 3'UTR (1477bp in length), and identify it as a potential target of nonsense-mediated decay.