Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• iScience, 2020-05, Vol.23 (5), p.101053, Article 101053

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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. [Display omitted] •Tropomyosin isoform Tpm3.1 co-localizes with the actin cytoskeleton in the AIS•Tpm3.1 inhibition led to a less organized AIS actin cytoskeleton•Perturbation of Tpm3.1 function reduced the accumulation of AIS scaffolding proteins•Tpm3.1 inhibition compromised cargo sorting and rapidly reduced firing frequency Biological Sciences; Molecular Neuroscience; Cellular Neuroscience; Cell Biology