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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

Sequential Rap1 activation by Cdk5 and Reelin signaling. Cdk5 and Reelin signaling activate Rap1 through the activation of different Rap1GEFs in the control of the radial migration of cortical neurons in the cerebral cortex in a sequential manner.
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Figure 3: Sequential Rap1 activation by Cdk5 and Reelin signaling. Cdk5 and Reelin signaling activate Rap1 through the activation of different Rap1GEFs in the control of the radial migration of cortical neurons in the cerebral cortex in a sequential manner.

Mentions: Rap1 signaling is involved in neuronal migration and is regulated by Cdk5 (Utreras et al., 2013). Rap1 activation promotes the cell-surface localization of N-cadherin (Jossin and Cooper, 2011). The N-cadherin-mediated adhesion complex is required for multipolar-bipolar transition (Jossin and Cooper, 2011) and radial fiber-dependent neuronal migration (Kawauchi et al., 2010). A previous study has shown that pharmacological inhibition of Cdk5 activity enhances N-cadherin-mediated cell-cell adhesion (Kwon et al., 2000). Rap1 activation depends upon Rap1-GEFs, including Rap1GEF1 (also known as C3G) and Rap1GEF2. RapGEF1 activation of Rap1 controls somal/terminal translocation triggered by Reelin (Franco et al., 2011; Jossin and Cooper, 2011; Sekine et al., 2012) via the stabilization of leading processes toward the marginal zone (Franco et al., 2011; Sekine et al., 2012). Interestingly, RapGEF2 KO mice showed a neuronal migration defect phenotype in the subcortical area, which indicated the involvement of RapGEF2 in multipolar-bipolar transition (Bilasy et al., 2009). Recently, Ye et al. have shown that Cdk5 phosphorylates RapGEF2 at Ser1124 and its phosphorylation is required for Rap1 activation (Ye et al., 2014). Previous studies have shown that RapGEF1-dependent Rap1 activation is dispensable in multipolar-bipolar transition (Sekine et al., 2012); therefore, Cdk5 mediated Rap1 activation via RapGEF2 phosphorylation is important for this transition. As proposed by Ye et al. (2014), the two pathways of Reelin and Cdk5 are not simply parallel, but rather act on successive phases of neuronal migration via Rap1 activation. Cdk5-mediated RapGEF2 phosphorylation controls multipolar-bipolar transition and Reelin-mediated RapGEF1 activation promotes terminal translocation (Figure 3). This idea fits well with our previous observations in mutant mice that lack Cdk5/p35 and Reelin/Dab1 (Ohshima et al., 2001, 2002; Ohshima and Mikoshiba, 2002).


Neuronal migration and protein kinases.

Ohshima T - Front Neurosci (2015)

Sequential Rap1 activation by Cdk5 and Reelin signaling. Cdk5 and Reelin signaling activate Rap1 through the activation of different Rap1GEFs in the control of the radial migration of cortical neurons in the cerebral cortex in a sequential manner.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 3: Sequential Rap1 activation by Cdk5 and Reelin signaling. Cdk5 and Reelin signaling activate Rap1 through the activation of different Rap1GEFs in the control of the radial migration of cortical neurons in the cerebral cortex in a sequential manner.
Mentions: Rap1 signaling is involved in neuronal migration and is regulated by Cdk5 (Utreras et al., 2013). Rap1 activation promotes the cell-surface localization of N-cadherin (Jossin and Cooper, 2011). The N-cadherin-mediated adhesion complex is required for multipolar-bipolar transition (Jossin and Cooper, 2011) and radial fiber-dependent neuronal migration (Kawauchi et al., 2010). A previous study has shown that pharmacological inhibition of Cdk5 activity enhances N-cadherin-mediated cell-cell adhesion (Kwon et al., 2000). Rap1 activation depends upon Rap1-GEFs, including Rap1GEF1 (also known as C3G) and Rap1GEF2. RapGEF1 activation of Rap1 controls somal/terminal translocation triggered by Reelin (Franco et al., 2011; Jossin and Cooper, 2011; Sekine et al., 2012) via the stabilization of leading processes toward the marginal zone (Franco et al., 2011; Sekine et al., 2012). Interestingly, RapGEF2 KO mice showed a neuronal migration defect phenotype in the subcortical area, which indicated the involvement of RapGEF2 in multipolar-bipolar transition (Bilasy et al., 2009). Recently, Ye et al. have shown that Cdk5 phosphorylates RapGEF2 at Ser1124 and its phosphorylation is required for Rap1 activation (Ye et al., 2014). Previous studies have shown that RapGEF1-dependent Rap1 activation is dispensable in multipolar-bipolar transition (Sekine et al., 2012); therefore, Cdk5 mediated Rap1 activation via RapGEF2 phosphorylation is important for this transition. As proposed by Ye et al. (2014), the two pathways of Reelin and Cdk5 are not simply parallel, but rather act on successive phases of neuronal migration via Rap1 activation. Cdk5-mediated RapGEF2 phosphorylation controls multipolar-bipolar transition and Reelin-mediated RapGEF1 activation promotes terminal translocation (Figure 3). This idea fits well with our previous observations in mutant mice that lack Cdk5/p35 and Reelin/Dab1 (Ohshima et al., 2001, 2002; Ohshima and Mikoshiba, 2002).

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