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Recently, Nature Communications published online the latest research progress of the researcher Bao Lan's group at the Center for Excellence in Molecular Cell Science (Institute of Biochemistry and Cell Biology) of the Chinese Academy of Sciences-α-TubK40me3 is required for neuronal polarization and migration by promoting microtubule formation
.
The study revealed that the newly discovered trimethylation modification on α-tubulin can promote the formation of microtubules, thereby regulating the establishment and migration of neuronal polarity
.
During the development of the cerebral cortex, new neurons need to migrate to a designated location to connect to the circuit.
This process is of great significance to the formation of the cerebral cortex
.
As a major cytoskeletal component in cells, microtubules play an important role in the migration of neurons
.
The dynamics of microtubules are regulated by a variety of post-translational modifications of tubulin
.
The previous research of the research group found that the acetylation modification on the 40th lysine of α-tubulin plays an important role in the development of the nervous system.
The lack of α-tubulin acetylation can cause defects in the migration of cortical neurons, and Lead to neuron overgrowth and branching phenotype (Li et al, J Neurosci, 2012; Wei et al, Cereb Cortex, 2018)
.
Studies have shown that there is also trimethylation catalyzed by SETD2 at the same site where α-tubulin acetylation is modified.
However, the academic circles are concerned about the regulation mechanism of α-tubulin trimethylation on the function of microtubules.
Its role in the development of the nervous system is still poorly understood
.
In this study, the researchers prepared an antibody that specifically recognizes the trimethylation modification of tubulin.
Through the antibody, it was detected that tubulin was in a hypermethylated state in the cerebral cortex on the 14th and 16th day of the mouse embryonic period.
.
Knockdown of SETD2 will affect the transition of cortical neurons from multipolar to bipolar state, resulting in defects in neuronal migration.
Knockdown of SETD2 in primary cultured neurons will also affect the establishment of neuronal polarity.
The above phenotypes It can be restored by expressing cytoplasmic localization of SETD2 truncated body and tubulin mutant that mimics trimethylation, indicating that α-tubulin trimethylation modification plays an important role in the process of neuron polarization and migration
.
In terms of mechanism research, the study found that the trimethylated α-tubulin is more likely to be distributed on the microtubules in the polymerized state, and can produce a sufficient number of microtubules in neurons by promoting the nucleation of tubulin To complete the establishment and conversion of the polarity
.
In addition, further studies have also found that there is a competitive cross-regulation between the trimethylation and acetylation of α-tubulin at the same site.
When the acetylation of α-tubulin is absent, the trimethylation is The increased level of modification may compensate for the role of acetylation modification in the development of the cerebral cortex
.
This study reveals the role and mechanism of alpha-tubulin trimethylation modification in the development of the nervous system, which will help expand and deepen the understanding of microtubule assembly and dynamic regulation in neurons in the academic community
.
The research work was funded by the National Natural Science Foundation of China, the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences, and the Shanghai Science and Technology Commission
.
The trimethylation modification of α-tubulin regulates the polarization and migration of neurons by promoting the formation of microtubules.
Source: Center for Excellence in Molecular and Cellular Science, Chinese Academy of Sciences
.
The study revealed that the newly discovered trimethylation modification on α-tubulin can promote the formation of microtubules, thereby regulating the establishment and migration of neuronal polarity
.
During the development of the cerebral cortex, new neurons need to migrate to a designated location to connect to the circuit.
This process is of great significance to the formation of the cerebral cortex
.
As a major cytoskeletal component in cells, microtubules play an important role in the migration of neurons
.
The dynamics of microtubules are regulated by a variety of post-translational modifications of tubulin
.
The previous research of the research group found that the acetylation modification on the 40th lysine of α-tubulin plays an important role in the development of the nervous system.
The lack of α-tubulin acetylation can cause defects in the migration of cortical neurons, and Lead to neuron overgrowth and branching phenotype (Li et al, J Neurosci, 2012; Wei et al, Cereb Cortex, 2018)
.
Studies have shown that there is also trimethylation catalyzed by SETD2 at the same site where α-tubulin acetylation is modified.
However, the academic circles are concerned about the regulation mechanism of α-tubulin trimethylation on the function of microtubules.
Its role in the development of the nervous system is still poorly understood
.
In this study, the researchers prepared an antibody that specifically recognizes the trimethylation modification of tubulin.
Through the antibody, it was detected that tubulin was in a hypermethylated state in the cerebral cortex on the 14th and 16th day of the mouse embryonic period.
.
Knockdown of SETD2 will affect the transition of cortical neurons from multipolar to bipolar state, resulting in defects in neuronal migration.
Knockdown of SETD2 in primary cultured neurons will also affect the establishment of neuronal polarity.
The above phenotypes It can be restored by expressing cytoplasmic localization of SETD2 truncated body and tubulin mutant that mimics trimethylation, indicating that α-tubulin trimethylation modification plays an important role in the process of neuron polarization and migration
.
In terms of mechanism research, the study found that the trimethylated α-tubulin is more likely to be distributed on the microtubules in the polymerized state, and can produce a sufficient number of microtubules in neurons by promoting the nucleation of tubulin To complete the establishment and conversion of the polarity
.
In addition, further studies have also found that there is a competitive cross-regulation between the trimethylation and acetylation of α-tubulin at the same site.
When the acetylation of α-tubulin is absent, the trimethylation is The increased level of modification may compensate for the role of acetylation modification in the development of the cerebral cortex
.
This study reveals the role and mechanism of alpha-tubulin trimethylation modification in the development of the nervous system, which will help expand and deepen the understanding of microtubule assembly and dynamic regulation in neurons in the academic community
.
The research work was funded by the National Natural Science Foundation of China, the Strategic Leading Science and Technology Project of the Chinese Academy of Sciences, and the Shanghai Science and Technology Commission
.
The trimethylation modification of α-tubulin regulates the polarization and migration of neurons by promoting the formation of microtubules.
Source: Center for Excellence in Molecular and Cellular Science, Chinese Academy of Sciences
