New Study Reveals the Critical Role of a α-tubulin Acetyltransferase in Neuronal Migration

Neuronal migration is a fundamental process during the development of the cerebral cortex and is regulated by cytoskeletal components including microtubles. Microtubule dynamics can be modulated by post-translational modifications to tubulin subunits. However，whether post-translational modifications of tubulins regulate neuronal migration remains to be defined. Now researchers from Chinese Academy of Sciences provide the first line of evidence that the acetyltransferase MEC-17 deficiency leads to α-tubulin acetylation and impaires migration of cortical neurons.

 

LI Lei and his colleagues, under the supervision of Dr. BAO Lan at the Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, used a series of in vivo, in vitro experiments to show that MEC-17 is critical for migration of cortical neurons. 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. Further experiments showed that loss of MEC-17 largely reduced the level of α-tubulin acetylation in cortical neurons. 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. This study demonstrates a critical role of MEC-17 and α-tubulin acetylation in the migration of cortical neurons, and also provides a cellular mechanism how post-translational modifications of tubulins regulate neuronal migration.

 

This work entitled “MEC-17 Deficiency Leads to Reduced α-Tubulin Acetylation and Impaired Migration of Cortical Neurons” was published in The Journal of Neuroscience on Sep 13^th, 2012. This study was supported by grants from Chinese Academy of Sciences, National Natural Science Foundation of China and Ministry of Science and Technology.

 

CONTACT:

BAO Lan

Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China

Tel: +86-21-5492-1369, E-mail: baolan@sibs.ac.cn

 

MEC-17 is highly expressed in the cortex during development, and regulates migration of cortical projection neurons. A, MEC-17 transcript distribution in the cerebral cortex. B, MEC-17 deficiency alters the radial migration of the cortical projection neurons. C, Loss of HDAC6 or overexpression of tubulinK40Q reduces the defects in MEC-17-deficient cortical projection neurons. (Image provided by Dr. BAO Lan)