SUMOylation controls the neurodevelopmental function of the transcription factor Zbtb20

AbstractSUMOylation is a dynamic post ‐translational protein modification that primarily takes place in cell nuclei, where it plays a key role in multiple DNA‐related processes. In neurons, the SUMOylation‐dependent control of a subset of neuronal transcription factors is known to regulate various aspects of nerve cell differentia tion, development, and function. In an unbiased screen for endogenous SUMOylation targets in the developing mouse brain, based on a His6‐HA‐SUMO1 KI mouse line, we previously identified the transcription factor Zbtb20 as a new SUMO1‐conjugate. We show here that the three key SUMO paralogues SUMO1, SUMO2, and SUMO3 can all be conjugated to Zbtb20in vitro in HEK293FT cells, and we confirm the SUMOylation of Zbtb20in vivo in mouse brain. Using primary hippocampal neurons from wild ‐type and Zbtb20 KO mice as a model system, we then demonstrate that the expression of Zbtb20 is required for proper nerve cell development and neurite growth and branching. Furthermore, we show that the SUMOylation of Zbtb20 is essential for its function in this context, and provide evidence indi cating that SUMOylation affects the Zbtb20‐dependent transcriptional profile of neurons. Our data highlight the role of SUMOylation in the regulation of neuronal transcription factors that determine nerve cell development, and they demonstrate that key functions of the transcription factor Zbtb20 in neuronal development and neurite growth are under obligatory SUMOyla...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research