RT Journal Article
SR Electronic
T1 Tropomyosin Tpm3.1 is required to maintain the structure and function of the axon initial segment
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 711614
DO 10.1101/711614
A1 Amr Abouelezz
A1 Holly Stefen
A1 Mikael Segerstråle
A1 David Micinski
A1 Rimante Minkeviciene
A1 Edna C. Hardeman
A1 Peter W. Gunning
A1 Casper C. Hoogenraad
A1 Tomi Taira
A1 Thomas Fath
A1 Pirta Hotulainen
YR 2019
UL http://biorxiv.org/content/early/2019/07/23/711614.abstract
AB The axon initial segment (AIS) is the site of action potential initiation and serves as a vesicular filter and diffusion barrier that help maintain neuronal polarity. Recent studies have revealed details about a specialized structural complex in the AIS. While an intact actin cytoskeleton is required for AIS formation, pharmacological disruption of actin polymerization compromises the AIS vesicle filter but does not affect overall AIS structure. In this study, we found that the tropomyosin isoform Tpm3.1 decorates a population of relatively stable actin filaments in the AIS. Inhibiting Tpm3.1 in cultured hippocampal neurons led to the loss of AIS structure, the AIS vesicle filter, the clustering of sodium ion channels, and reduced firing frequency. We propose that Tpm3.1-decorated actin filaments form a stable actin filament network under the AIS membrane which provides a scaffold for membrane organization and AIS proteins.