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

• DOI: 10.1016/j.isci.2020.101053
• Publication Date: 2020-04-12T14:24:02Z
• Authors: 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
• Keywords: 0301 basic medicine; Science; MOLECULAR COMPOSITION; 610; ISOFORMS; 3101 Biochemistry and Cell Biology; Article; 03 medical and health sciences; anzsrc-for: 31 Biological Sciences; General; SPECTRIN; MYOSIN-II ACTIVITY; Biochemistry, cell and molecular biology; ta113; 0303 health sciences; anzsrc-for: 3101 Biochemistry and Cell Biology; BINDING PROTEINS; Q; Neurosciences; ACTIN CYTOSKELETON; ANKYRIN-G; Cell Biology; Biological Sciences; MAINTENANCE; MEMBRANE SKELETON; Cellular Neuroscience; POLARIZED CARGO TRANSPORT; Molecular Neuroscience; 31 Biological Sciences

ABSTRACTThe 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.