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

doi:10.1016/j.isci.2020.101053

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

Department of Computer Science

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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 language	English
Article number	101053
Number of pages	50
Journal	iScience
Volume	23
Issue number	5
DOIs	https://doi.org/10.1016/j.isci.2020.101053
Publication status	Published - 22 May 2020
MoE publication type	A1 Journal article-refereed

Keywords

Biological Sciences
Cell Biology
Cellular Neuroscience
Molecular Neuroscience

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

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.",

keywords = "Biological Sciences, Cell Biology, Cellular Neuroscience, Molecular Neuroscience",

author = "Amr Abouelezz and Holly Stefen and Mikael Segerstr{\aa}le and David Micinski and Rimante Minkeviciene and Lauri Lahti and Hardeman, {Edna C.} and Gunning, {Peter W.} and Hoogenraad, {Casper C.} and Tomi Taira and Thomas Fath and Pirta Hotulainen",

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Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment. / Abouelezz, Amr; Stefen, Holly; Segerstråle, Mikael; Micinski, David; Minkeviciene, Rimante; Lahti, Lauri; Hardeman, Edna C.; Gunning, Peter W.; Hoogenraad, Casper C.; Taira, Tomi; Fath, Thomas; Hotulainen, Pirta.

In: iScience, Vol. 23, No. 5, 101053, 22.05.2020.

Research output: Contribution to journal › Article › Scientific › peer-review

TY - JOUR

T1 - Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment

AU - Abouelezz, Amr

AU - Stefen, Holly

AU - Segerstråle, Mikael

AU - Micinski, David

AU - Minkeviciene, Rimante

AU - Lahti, Lauri

AU - Hardeman, Edna C.

AU - Gunning, Peter W.

AU - Hoogenraad, Casper C.

AU - Taira, Tomi

AU - Fath, Thomas

AU - Hotulainen, Pirta

PY - 2020/5/22

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

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