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Arp2/3 Is Required for Axonal Arbor Terminal Retraction in Cerebellar Granule Neurons

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Abstract

Although selective pruning of subsets of branches is a key step for axonal remodeling, the underlying mechanisms have not fully elucidated. We have reported that the retraction rate of axonal arbor is higher in the terminals, where less kinesin is sorted, and inhibiting actin turnover by treatment with latrunculin A prevented retraction in such terminals. In the present study, we investigated the effects of pharmacological inhibitors for the regulators of actin polymerization/destabilization on the elongation and retraction of arbor terminals in cerebellar granule neurons. Inhibition of an actin nucleator Arp2/3 with CK-666 or CK-869 inhibited the retraction of arbor terminals. However, inhibitors for PAK/LIMK, upstream signaling of ADF/cofilin, reduced the elongation rate but not the retraction rate. A photoconversion analysis revealed that turnover of F-actin at the tip of the axonal terminal is faster in the presence of the Arp2/3 inhibitor compared with the control and neurons treated with the LIMK inhibitor. Our results indicate the important role of Arp2/3 for the retraction of axonal arbor terminals in cerebellar granule neurons.

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ACKNOWLEDGMENTS

We thank Dr. Michael Davidson for providing the constructs used in this study.

Funding

This study was funded by grants from the JSPS KAKENHI Grant (no. 17K07107).

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Authors and Affiliations

  1. Department of Human and Artificial Intelligence Systems, Faculty of Engineering, University of Fukui, 3-9-1 Bunkyo, 910-8507, Fukui, Japan

    T. Ikeno

  2. Department of Applied Chemistry and Biotechnology, Faculty of Engineering, University of Fukui, Fukui, Japan

    Y. Konishi

  3. Life Science Innovation Center, University of Fukui, Fukui, Japan

    Y. Konishi

Authors
  1. T. Ikeno
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  2. Y. Konishi
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Correspondence to Y. Konishi.

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Conflict of interest. The authors declare no conflicts of interest associated with this manuscript.

Ethical approval. All animals were treated according to the ethical guidelines from the Central Institute for Experimental Animals (CIEA, Japan). The experimental protocols were approved by the animal experiment committee of the University of Fukui.

Additional information

Abbreviations: Arp, actin-related protein; PAK, p21-activated kinase; LIMK, LIM kinase; ADF, actin-depolymerizing factor; CGN, cerebellar granule neuron; DMSO; dimethyl sulfoxide; MEM, minimal essential medium.

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Ikeno, T., Konishi, Y. Arp2/3 Is Required for Axonal Arbor Terminal Retraction in Cerebellar Granule Neurons. Neurochem. J. 14, 32–36 (2020). https://doi.org/10.1134/S1819712420010109

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  • DOI: https://doi.org/10.1134/S1819712420010109

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