Characterization of the striatal kinase Dclk3 and its neuroprotective effects againstmutant huntingtin

Abstract

International audienceDouble-cortin-like kinases (Dclks) play major roles in development and maintenance of neuronal functions. The neurobiological role of the third member of this family, the striatal-enriched Dclk3 is unknown. We characterized the cytoplasmic and nuclear localization of Dclk3 in the striatum in non-human primates and in man. A yeast-two hybrid screen identified seven Dclk3 interactors, all possessing zinc finger domains. One candidate is known to regulate many transcription activating factors (TAFs), p53 and lysine acetyl transferases. In line with this, expression of Dclk3 kinase domain in human striatal neural stem cells produces transcriptional changes that are mainly linked to chromatin remodeling. Chromatin and transcriptional perturbations have been described in 4/6/202