Neuronal migration and protein kinases

Toshio Ohshima

doi:10.3389/fnins.2014.00458

Abstract

The formation of the six-layered structure of the mammalian cortex via the inside-out pattern of neuronal migration is fundamental to neocortical functions. Extracellular cues such as Reelin induce intracellular signaling cascades through the protein phosphorylation. Migrating neurons also have intrinsic machineries to regulate cytoskeletal proteins and adhesion properties. Protein phosphorylation regulates these processes. Moreover, the balance between phosphorylation and dephosphorylation is modified by extracellular cues. Multipolar-bipolar transition, radial glia-guided locomotion and terminal translocation are critical steps of radial migration of cortical pyramidal neurons. Protein kinases such as Cyclin-dependent kinase 5 (Cdk5) and c-Jun N-terminal kinases (JNKs) involve these steps. In this review, I shall give an overview the roles of protein kinases in neuronal migration.

Highlights

The formation of the six-layered structure of the mammalian cortex via the inside-out pattern of neuronal migration is fundamental to neocortical functions
The sixlayered structure of the mammalian cerebral cortex is formed by coordinated neuronal migration via inside-out patterning
Microtubule- and actin-associated proteins regulate the dynamics of microtubule and actin cytoskeletons during neuronal migration; deletions and mutations of crucial genes involved in cytoskeletal processes lead to human lissencephaly (Dobyns, 1987) and mouse mutants with a neuronal migration phenotype

Summary

Introduction

The formation of the six-layered structure of the mammalian cortex via the inside-out pattern of neuronal migration is fundamental to neocortical functions. LESSONS FROM THE HUMAN DISORDER LISSENCEPHALY Failure of neuronal migration causes severe developmental abnormalities in the layering of the cerebral cortex and results in the human disorder lissencephaly, which means “smooth brain.” Microtubule- and actin-associated proteins regulate the dynamics of microtubule and actin cytoskeletons during neuronal migration; deletions and mutations of crucial genes involved in cytoskeletal processes lead to human lissencephaly (Dobyns, 1987) and mouse mutants with a neuronal migration phenotype. DCX function is modulated by its phosphorylation by several kinases in site specific manner, including Microtubule affinity-regulating kinase 2 (MARK2), Protein kinase A (PKA), Cyclin-dependent kinase 5 (Cdk5), and c-Jun Nterminal kinases (JNKs) (Figure 1).

Results

Conclusion