Bao, L (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Cell Biol, Shanghai 200031, Peoples R China.,email@example.com
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 alpha-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 alpha-tubulin acetyltransferase that has been found to play a major role in the acetylation of alpha-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 alpha-tubulin deacetylase HDAC6 or overexpression of tubulin(K40Q) to mimic acetylated alpha-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 alpha-tubulin, appears to control the migration and morphological transition of cortical neurons. This finding reveals the importance of MEC-17 and alpha-tubulin acetylation in cortical development.