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Neuronal migration and protein kinases.

Ohshima T - Front Neurosci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University Tokyo, Japan.

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.

No MeSH data available.


Related in: MedlinePlus

Functions of Cdk5 in neuronal migration. Cdk5 is required for the radial migration of later-generated neurons in the cerebral cortex. Cdk5 is necessary for multipolar-to-bipolar transition (Step 1) and locomotion through the regulation of nucleokinesis of migrating neurons (Step 2). For these steps, Cdk5 regulates the dynamics of microtubules-cytoskeleton, actin-cytoskeleton and cell-adhesion through the phosphorylation of its substrate proteins.
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Figure 2: Functions of Cdk5 in neuronal migration. Cdk5 is required for the radial migration of later-generated neurons in the cerebral cortex. Cdk5 is necessary for multipolar-to-bipolar transition (Step 1) and locomotion through the regulation of nucleokinesis of migrating neurons (Step 2). For these steps, Cdk5 regulates the dynamics of microtubules-cytoskeleton, actin-cytoskeleton and cell-adhesion through the phosphorylation of its substrate proteins.

Mentions: Cdk5 is serine/threonine kinase and its high activity is detected in post-mitotic neurons. Cdk5 forms heterodimer with its activating subunits, p35 or p39. The involvement of Cdk5 in neuronal migration was revealed by the analyses of Cdk5KO mice (Ohshima et al., 1996; Gilmore et al., 1998). Cdk5KO mice lack the laminar structure of the cerebral cortex (Ohshima et al., 1996). Birth-date labeling of the embryonic brain showed profound migration defects in cortical neurons (Gilmore et al., 1998). p35KO mice have milder abnormalities in neuronal migration (Chae et al., 1997). The identical phenotype of double-knockout p35/p39 mice and Cdk5KO mice indicates the redundant function of p35 and p39 (Ko et al., 2001). Conditional Cdk5KO mice showed an inverted cortical layer structure in layers II–VI (Ohshima et al., 2007). Cdk5 regulates multiple steps of radial migration of cortical neurons during the locomotion mode of migration (Figure 2). These include the transition from multipolar to bipolar morphology in the IZ (Ohshima et al., 2007), formation of leading processes (Kawauchi et al., 2006), and formation of a cytoplasmic dilation/swelling, which is a structure specific to migrating neurons, at the proximal region of the leading process (Nishimura et al., 2014).


Neuronal migration and protein kinases.

Ohshima T - Front Neurosci (2015)

Functions of Cdk5 in neuronal migration. Cdk5 is required for the radial migration of later-generated neurons in the cerebral cortex. Cdk5 is necessary for multipolar-to-bipolar transition (Step 1) and locomotion through the regulation of nucleokinesis of migrating neurons (Step 2). For these steps, Cdk5 regulates the dynamics of microtubules-cytoskeleton, actin-cytoskeleton and cell-adhesion through the phosphorylation of its substrate proteins.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4292441&req=5

Figure 2: Functions of Cdk5 in neuronal migration. Cdk5 is required for the radial migration of later-generated neurons in the cerebral cortex. Cdk5 is necessary for multipolar-to-bipolar transition (Step 1) and locomotion through the regulation of nucleokinesis of migrating neurons (Step 2). For these steps, Cdk5 regulates the dynamics of microtubules-cytoskeleton, actin-cytoskeleton and cell-adhesion through the phosphorylation of its substrate proteins.
Mentions: Cdk5 is serine/threonine kinase and its high activity is detected in post-mitotic neurons. Cdk5 forms heterodimer with its activating subunits, p35 or p39. The involvement of Cdk5 in neuronal migration was revealed by the analyses of Cdk5KO mice (Ohshima et al., 1996; Gilmore et al., 1998). Cdk5KO mice lack the laminar structure of the cerebral cortex (Ohshima et al., 1996). Birth-date labeling of the embryonic brain showed profound migration defects in cortical neurons (Gilmore et al., 1998). p35KO mice have milder abnormalities in neuronal migration (Chae et al., 1997). The identical phenotype of double-knockout p35/p39 mice and Cdk5KO mice indicates the redundant function of p35 and p39 (Ko et al., 2001). Conditional Cdk5KO mice showed an inverted cortical layer structure in layers II–VI (Ohshima et al., 2007). Cdk5 regulates multiple steps of radial migration of cortical neurons during the locomotion mode of migration (Figure 2). These include the transition from multipolar to bipolar morphology in the IZ (Ohshima et al., 2007), formation of leading processes (Kawauchi et al., 2006), and formation of a cytoplasmic dilation/swelling, which is a structure specific to migrating neurons, at the proximal region of the leading process (Nishimura et al., 2014).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University Tokyo, Japan.

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.

No MeSH data available.


Related in: MedlinePlus