Abstract
The Elongator complex is required for proper development of the cerebral cortex. Interfering with its activity in vivo delays the migration of postmitotic projection neurons, at least through a defective α-tubulin acetylation. However, this complex is already expressed by cortical progenitors where it may regulate the early steps of migration by targeting additional proteins. Here we report that connexin-43 (Cx43), which is strongly expressed by cortical progenitors and whose depletion impairs projection neuron migration, requires Elongator expression for its proper acetylation. Indeed, we show that Cx43 acetylation is reduced in the cortex of Elp3cKO embryos, as well as in a neuroblastoma cell line depleted of Elp1 expression, suggesting that Cx43 acetylation requires Elongator in different cellular contexts. Moreover, we show that histones deacetylase 6 (HDAC6) is a deacetylase of Cx43. Finally, we report that acetylation of Cx43 regulates its membrane distribution in apical progenitors of the cerebral cortex.
Highlights
The neocortex is a highly organized structure made of six distinct neuronal layers, which differ in terms of connectivity and gene expression profile (Molyneaux et al, 2007)
We further show that depletion of Elongator in vivo impairs the acetylation of Cx43, suggesting that Elp3 promotes Cx43 acetylation in the developing cerebral cortex
We previously reported that Elongator controls the radial migration of projection neurons partly through α-tubulin acetylation (Creppe et al, 2009)
Summary
The neocortex is a highly organized structure made of six distinct neuronal layers, which differ in terms of connectivity and gene expression profile (Molyneaux et al, 2007). Besides its central role as a tRNA-modifying protein (Ladang et al, 2015; Laguesse et al, 2015; Delaunay et al, 2016), Elp has been shown to Proper Connexin-43 Acetylation Requires Elp regulate the acetylation of three proteins: histone H3 in the nucleus (Winkler et al, 2002), bruchpilot at the drosophila neuromuscular junction (Miskiewicz et al, 2011) and α-tubulin in migrating post-mitotic projection neurons (Creppe et al, 2009). We previously showed that reducing Elongator activity in post-mitotic neurons correlates with reduced α-tubulin acetylation and impaired migration to the CP (Creppe et al, 2009). As Elongator subunits are found in the VZ/SVZ of the developing cortex (Creppe et al, 2009; Laguesse et al, 2015), we hypothesized that other targets of Elongator (direct or indirect) play a role in the regulation of early steps of migration, contributing to the overall migration impairment observed after depletion of Elongator
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
