Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment

Amr Abouelezz, Holly Stefen, Mikael Segerstråle, David Micinski, Rimante Minkeviciene, Lauri Lahti, Edna C. Hardeman, Peter W. Gunning, Casper C. Hoogenraad, Tomi Taira, Thomas Fath, Pirta Hotulainen*

*Corresponding author for this work

Research output: Contribution to journalArticleScientificpeer-review

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Abstract

The axon initial segment (AIS) is the site of action potential initiation and serves as a cargo transport filter and diffusion barrier that helps maintain neuronal polarity. The AIS actin cytoskeleton comprises actin patches and periodic sub-membranous actin rings. We demonstrate that tropomyosin isoform Tpm3.1 co-localizes with actin patches and that the inhibition of Tpm3.1 led to a reduction in the density of actin patches. Furthermore, Tpm3.1 showed a periodic distribution similar to sub-membranous actin rings but Tpm3.1 was only partially congruent with sub-membranous actin rings. Nevertheless, the inhibition of Tpm3.1 affected the uniformity of the periodicity of actin rings. Furthermore, Tpm3.1 inhibition led to reduced accumulation of AIS structural and functional proteins, disruption in sorting somatodendritic and axonal proteins, and a reduction in firing frequency. These results show that Tpm3.1 is necessary for the structural and functional maintenance of the AIS.

Original languageEnglish
Article number101053
JournaliScience
Volume23
Issue number5
DOIs
Publication statusPublished - 22 May 2020
MoE publication typeA1 Journal article-refereed

Keywords

  • Biological Sciences
  • Cell Biology
  • Cellular Neuroscience
  • Molecular Neuroscience

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    Abouelezz, A., Stefen, H., Segerstråle, M., Micinski, D., Minkeviciene, R., Lahti, L., Hardeman, E. C., Gunning, P. W., Hoogenraad, C. C., Taira, T., Fath, T., & Hotulainen, P. (2020). Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment. iScience, 23(5), [101053]. https://doi.org/10.1016/j.isci.2020.101053