title: MEC-17 deficiency leads to reduced α-tubulin acetylation and impaired migration of cortical neurons.
abstract: Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components. Microtubule dynamics can be modulated by posttranslational modifications to tubulin subunits. Acetylation of α-tubulin at lysine 40 is important in regulating microtubule properties, and this process is controlled by acetyltransferase and deacetylase. MEC-17 is a newly discovered α-tubulin acetyltransferase that has been found to play a major role in the acetylation of α-tubulin in different species in vivo. However, the physiological function of MEC-17 during neural development is largely unknown. Here, we report that MEC-17 is critical for the migration of cortical neurons in the rat. MEC-17 was strongly expressed in the cerebral cortex during development. MEC-17 deficiency caused migratory defects in the cortical projection neurons and interneurons, and perturbed the transition of projection neurons from the multipolar stage to the unipolar/bipolar stage in the intermediate zone of the cortex. Furthermore, knockdown of α-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated α-tubulin could reduce the migratory and morphological defects caused by MEC-17 deficiency in cortical projection neurons. Thus, MEC-17, which regulates the acetylation of α-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and α-tubulin acetylation in cortical development.
authors.affiliation: State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Wei
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Pan
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000378:metabolism*; D000375:Aging / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014404:Tubulin / Q000378:metabolism*
chemical_list: D014404:Tubulin; D000123:Acetyltransferases