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Sliding of centrosome-unattached microtubules defines key features of neuronal phenotype

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ABSTRACT

Rao et al. show that during migration, neurons contain a small population of centrosome-unattached microtubules in the leading process that are capable of sliding. Increasing the proportion of centrosome-unattached microtubules alters neuronal morphology, migration path, and microtubule behavior in the leading process.

No MeSH data available.


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Schematic summary of MT sliding scenarios in experiments on migratory neurons and the effects on neuronal morphology, migration, and MTs in the leading process. Neurons treated with control siRNA display a minimal amount of sliding (green MT = sliding MT), tortuosity, and MT buckling and migrate in a smooth, consistent path (straight green arrow). When FCPT is used to prevent MT sliding (represented by X), MTs in the leading process of control siRNA-treated neurons show an increase in MT buckling (but do not become tortuous), and their migration path is irregular (curved green arrow). After treatment with ninein siRNA, MT buckling is observed, the leading process becomes tortuous, and migration is compromised (small green arrow). When FCTP is applied to the ninein-depleted neurons, MT buckling and tortuosity are exacerbated, and neuron movement is restored (but with abnormalities in migration path).
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fig8: Schematic summary of MT sliding scenarios in experiments on migratory neurons and the effects on neuronal morphology, migration, and MTs in the leading process. Neurons treated with control siRNA display a minimal amount of sliding (green MT = sliding MT), tortuosity, and MT buckling and migrate in a smooth, consistent path (straight green arrow). When FCPT is used to prevent MT sliding (represented by X), MTs in the leading process of control siRNA-treated neurons show an increase in MT buckling (but do not become tortuous), and their migration path is irregular (curved green arrow). After treatment with ninein siRNA, MT buckling is observed, the leading process becomes tortuous, and migration is compromised (small green arrow). When FCTP is applied to the ninein-depleted neurons, MT buckling and tortuosity are exacerbated, and neuron movement is restored (but with abnormalities in migration path).

Mentions: In summary, the results of our study indicate that only very limited sliding of MTs occurs during neuronal migration and that what little sliding occurs is important for fine-tuning the morphology and migratory behavior of the neuron. In addition, our results indicate that neuronal phenotype is defined in part by the degree of MT sliding permitted by the relative proportions of centrosome-attached and centrosome-unattached MTs. On the basis of our results, summarized in Fig. 8, we would conclude that motor-driven forces exist in the neuron that can drive MT sliding, but these forces are limited in their capacity to do so by attachment of the MTs to the centrosome as well as by regulatable brakes on sliding imposed by proteins such as kinesin-5. The degree of MT sliding in turn influences the migratory behavior of the neuron as well as process length and morphology. We speculate that when all of the MTs are centrosome-detached and especially when they are severed into shorter pieces, MTs can slide to a far greater degree than in any of our experimental scenarios, thus enabling a bona fide axon to grow longer and longer, without tugging along the soma. These ideas are buoyed by the fact that the same motor protein that predominantly transports MTs in the axon, namely cytoplasmic dynein (Ahmad et al., 1998, 2006; He et al., 2005), is also the predominant force-generating motor on MTs during neuronal migration (Xiang et al., 1994; Sheeman et al., 2003; Shu et al., 2004; Tanaka et al., 2004; Tsai and Gleeson, 2005; Willemsen et al., 2012).


Sliding of centrosome-unattached microtubules defines key features of neuronal phenotype
Schematic summary of MT sliding scenarios in experiments on migratory neurons and the effects on neuronal morphology, migration, and MTs in the leading process. Neurons treated with control siRNA display a minimal amount of sliding (green MT = sliding MT), tortuosity, and MT buckling and migrate in a smooth, consistent path (straight green arrow). When FCPT is used to prevent MT sliding (represented by X), MTs in the leading process of control siRNA-treated neurons show an increase in MT buckling (but do not become tortuous), and their migration path is irregular (curved green arrow). After treatment with ninein siRNA, MT buckling is observed, the leading process becomes tortuous, and migration is compromised (small green arrow). When FCTP is applied to the ninein-depleted neurons, MT buckling and tortuosity are exacerbated, and neuron movement is restored (but with abnormalities in migration path).
© Copyright Policy - openaccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4862329&req=5

fig8: Schematic summary of MT sliding scenarios in experiments on migratory neurons and the effects on neuronal morphology, migration, and MTs in the leading process. Neurons treated with control siRNA display a minimal amount of sliding (green MT = sliding MT), tortuosity, and MT buckling and migrate in a smooth, consistent path (straight green arrow). When FCPT is used to prevent MT sliding (represented by X), MTs in the leading process of control siRNA-treated neurons show an increase in MT buckling (but do not become tortuous), and their migration path is irregular (curved green arrow). After treatment with ninein siRNA, MT buckling is observed, the leading process becomes tortuous, and migration is compromised (small green arrow). When FCTP is applied to the ninein-depleted neurons, MT buckling and tortuosity are exacerbated, and neuron movement is restored (but with abnormalities in migration path).
Mentions: In summary, the results of our study indicate that only very limited sliding of MTs occurs during neuronal migration and that what little sliding occurs is important for fine-tuning the morphology and migratory behavior of the neuron. In addition, our results indicate that neuronal phenotype is defined in part by the degree of MT sliding permitted by the relative proportions of centrosome-attached and centrosome-unattached MTs. On the basis of our results, summarized in Fig. 8, we would conclude that motor-driven forces exist in the neuron that can drive MT sliding, but these forces are limited in their capacity to do so by attachment of the MTs to the centrosome as well as by regulatable brakes on sliding imposed by proteins such as kinesin-5. The degree of MT sliding in turn influences the migratory behavior of the neuron as well as process length and morphology. We speculate that when all of the MTs are centrosome-detached and especially when they are severed into shorter pieces, MTs can slide to a far greater degree than in any of our experimental scenarios, thus enabling a bona fide axon to grow longer and longer, without tugging along the soma. These ideas are buoyed by the fact that the same motor protein that predominantly transports MTs in the axon, namely cytoplasmic dynein (Ahmad et al., 1998, 2006; He et al., 2005), is also the predominant force-generating motor on MTs during neuronal migration (Xiang et al., 1994; Sheeman et al., 2003; Shu et al., 2004; Tanaka et al., 2004; Tsai and Gleeson, 2005; Willemsen et al., 2012).

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Rao et al. show that during migration, neurons contain a small population of centrosome-unattached microtubules in the leading process that are capable of sliding. Increasing the proportion of centrosome-unattached microtubules alters neuronal morphology, migration path, and microtubule behavior in the leading process.

No MeSH data available.


Related in: MedlinePlus