Loss of Elp3 Impairs the Acetylation and Distribution of Connexin-43 in the Developing Cerebral Cortex

Frontiers in Cellular Neuroscience
Sophie LaguesseLaurent Nguyen

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.

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Citations

Sep 30, 2017·FEBS Letters·Maria I DaudenSebastian Glatt
Aug 12, 2018·Nature Communications·Marija KojicBrandon J Wainwright
Feb 9, 2019·Nature Communications·Ting-Yu LinSebastian Glatt
Feb 6, 2020·Frontiers in Pharmacology·Raúl Lagos-CabréLisette Leyton
Nov 7, 2020·International Journal of Molecular Sciences·Nour-El-Hana AbbassiTing-Yu Lin

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Methods Mentioned

BETA
acetylation
genotyping
PCR
Transfections
transfection
confocal microscopy
Immunoprecipitation
ubiquitination

Software Mentioned

Primer3
GraphPad
graphPad Prism
ImageJ

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