Faculty Opinions recommendation of Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments.

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.

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Networks of Polarized Actin Filaments in the Axon Initial Segment Provide a Mechanism for Sorting Axonal and Dendritic Proteins

Cell Reports ◽

10.1016/j.celrep.2012.11.015 ◽

2012 ◽

Vol 2 (6) ◽

pp. 1546-1553 ◽

Cited By ~ 73

Author(s):

Kaori Watanabe ◽

Sarmad Al-Bassam ◽

Yusuke Miyazaki ◽

Thomas J. Wandless ◽

Paul Webster ◽

...

Keyword(s):

Actin Filaments ◽

Initial Segment ◽

Axon Initial Segment

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Axon Initial Segment Cytoskeleton: Architecture, Development, and Role in Neuron Polarity

Neural Plasticity ◽

10.1155/2016/6808293 ◽

2016 ◽

Vol 2016 ◽

pp. 1-19 ◽

Cited By ~ 76

Author(s):

Steven L. Jones ◽

Tatyana M. Svitkina

Keyword(s):

Actin Filaments ◽

Initial Segment ◽

Structural Features ◽

Axon Initial Segment ◽

Action Potential Firing ◽

Potential Firing ◽

Triangular Network ◽

Specialized Structure ◽

Architecture Development ◽

Neuron Polarity

The axon initial segment (AIS) is a specialized structure in neurons that resides in between axonal and somatodendritic domains. The localization of the AIS in neurons is ideal for its two major functions: it serves as the site of action potential firing and helps to maintain neuron polarity. It has become increasingly clear that the AIS cytoskeleton is fundamental to AIS functions. In this review, we discuss current understanding of the AIS cytoskeleton with particular interest in its unique architecture and role in maintenance of neuron polarity. The AIS cytoskeleton is divided into two parts, submembrane and cytoplasmic, based on localization, function, and molecular composition. Recent studies using electron and subdiffraction fluorescence microscopy indicate that submembrane cytoskeletal components (ankyrin G,βIV-spectrin, and actin filaments) form a sophisticated network in the AIS that is conceptually similar to the polygonal/triangular network of erythrocytes, with some important differences. Components of the AIS cytoplasmic cytoskeleton (microtubules, actin filaments, and neurofilaments) reside deeper within the AIS shaft and display structural features distinct from other neuronal domains. We discuss how the AIS submembrane and cytoplasmic cytoskeletons contribute to different aspects of AIS polarity function and highlight recent advances in understanding their AIS cytoskeletal assembly and stability.

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Axon initial segment cytoskeleton comprises a multiprotein submembranous coat containing sparse actin filaments

The Journal of Cell Biology ◽

10.1083/jcb.201401045 ◽

2014 ◽

Vol 205 (1) ◽

pp. 67-81 ◽

Cited By ~ 68

Author(s):

Steven L. Jones ◽

Farida Korobova ◽

Tatyana Svitkina

Keyword(s):

Actin Filaments ◽

Hippocampal Neurons ◽

Initial Segment ◽

Neuronal Cell ◽

Axon Initial Segment ◽

Actin Dynamics ◽

Neuronal Cell Adhesion Molecule ◽

Voltage Gated Sodium Channels ◽

Actin Structure ◽

Action Potential Initiation

The axon initial segment (AIS) of differentiated neurons regulates action potential initiation and axon–dendritic polarity. The latter function depends on actin dynamics, but actin structure and functions at the AIS remain unclear. Using platinum replica electron microscopy (PREM), we have characterized the architecture of the AIS cytoskeleton in mature and developing hippocampal neurons. The AIS cytoskeleton assembly begins with bundling of microtubules and culminates in formation of a dense, fibrillar–globular coat over microtubule bundles. Immunogold PREM revealed that the coat contains a network of known AIS proteins, including ankyrin G, spectrin βIV, neurofascin, neuronal cell adhesion molecule, voltage-gated sodium channels, and actin filaments. Contrary to existing models, we find neither polarized actin arrays, nor dense actin meshworks in the AIS. Instead, the AIS contains two populations of sparse actin filaments: short, stable filaments and slightly longer dynamic filaments. We propose that stable actin filaments play a structural role for formation of the AIS diffusion barrier, whereas dynamic actin may promote AIS coat remodeling.

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