Structure and Function of an Actin-Based Filter in the Proximal Axon

Balasanyan, Varuzhan; Watanabe, Kaori; Dempsey, William P.; Lewis, Tommy L.; Arnold, Don W.

doi:10.1016/j.celrep.2017.11.046

Cited by 41 publications

(57 citation statements)

References 29 publications

(48 reference statements)

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“…Several studies highlight the role of myosin as a tether, aiding in positioning of organelles along the neuronal process such as, at the axon initial segment (AIS), in axons and in dendrites. The AIS is an actin‐rich region that aids in halting dendritic cargo (Balasanyan et al, ; K. Watanabe et al, ). Specifically Myosin V motors present at the AIS cause stalling of dendritic cargo at the actin‐enriched AIS of neurons in culture (Al‐Bassam et al, ; Janssen et al, ) (Figure b).…”

Section: Actin In Organelle Dockingmentioning

confidence: 99%

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Role of actin in organelle trafficking in neurons

2019

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Actin is a major cytoskeletal element involved in multiple cellular processes. Actin‐rich regions present along the neuronal process aid in neuronal function, mediating multiple events involved in organelle trafficking. Actin is involved in organelle biogenesis, transport, and anchoring at specific locations. These functions can potentially be regulated by actin in a myosin‐dependent or myosin‐independent manner. The actin network could aid in membrane remodeling through membrane constriction, motor dependent transport, polymerization‐based transport, cargo anchoring, and halting of cargo by acting as a physical barrier. Additionally, actin dynamics is perturbed in some neurodegenerative diseases where it could impact organelle biogenesis, transport, or anchoring thereby contributing to progression of disease phenotypes. The role of actin and myosin in organelle trafficking is the primary focus of this review.

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Section: Actin In Organelle Dockingmentioning

confidence: 99%

Section: Organelle Tethering By Myosin Motorsmentioning

confidence: 99%

Role of actin in organelle trafficking in neurons

2019

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“…Previous studies revealed that, in addition to sub-membranous actin rings, actin forms patches in the AIS (Balasanyan et al, 2017;D'Este et al, 2015;Janssen et al, 2017;Jones et al, 2014;Leterrier et al, 2015;Watanabe et al, 2012;Xu et al, 2013;Zhong et al, 2014) that may play a role in presynaptic terminals (D'Este et al, 2015) or in the filtering of vesicles carrying somatodendritic cargo (Balasanyan et al, 2017;Janssen et al, 2017;Watanabe et al, 2012). However, little is known about the dynamics and regulation of these actin patches.…”

Section: The Ais Contains Patches Of F-actin With a Low Rate Of Depolmentioning

confidence: 99%

“…Somatodendritic cargo entering the AIS halt at regions of high F-actin concentration, in a process that is dependent on myosin motors (Balasanyan et al, 2017;Janssen et al, 2017;Watanabe et al, 2012 . 6b).…”

Section: Tpm31 Is Necessary For Maintaining the Selectivity Of Axonamentioning

confidence: 99%

“…Platinum replica electron microscopy showed that the AIS contains both short, stable actin filaments, as well as longer, dynamic filaments (Jones et al, 2014). Actin-based myosin motors play a role in the targeted delivery of somatodendritic and axonal vesicles (Janssen et al, 2017;Lewis et al, 2011;Lewis et al, 2009), and actin filaments form patches in the AIS (Balasanyan et al, 2017;Watanabe et al, 2012) that may serve as vesicle filters (Janssen et al, 2017;Leterrier and Dargent, 2014;Watanabe et al, 2012). While actin patches are not exclusive to the AIS, AIS actin patches are more stable than patches along the distal axon; the washing away of diffuse molecules by cell permeabilization led to the loss of actin patches in the distal axon, but not in the AIS (Watanabe et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

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Tropomyosin Tpm3.1 is required to maintain the structure and function of the axon initial segment

Abouelezz

Stefen

Segerstråle

et al. 2019

Preprint

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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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Formin Activity and mDia1 Contribute to Maintain Axon Initial Segment Composition and Structure

et al. 2021

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The axon initial segment (AIS) is essential for maintaining neuronal polarity, modulating protein transport into the axon, and action potential generation. These functions are supported by a distinctive actin and microtubule cytoskeleton that controls axonal trafficking and maintains a high density of voltage-gated ion channels linked by scaffold proteins to the AIS cytoskeleton. However, our knowledge of the mechanisms and proteins involved in AIS cytoskeleton regulation to maintain or modulate AIS structure is limited. In this context, formins play a significant role in the modulation of actin and microtubules. We show that pharmacological inhibition of formins modifies AIS actin and microtubule characteristics in cultured hippocampal neurons, reducing F-actin density and decreasing microtubule acetylation. Moreover, formin inhibition diminishes sodium channels, ankyrinG and βIV-spectrin AIS density, and AIS length, in cultured neurons and brain slices, accompanied by decreased neuronal excitability. We show that genetic downregulation of the mDia1 formin by interference RNAs also decreases AIS protein density and shortens AIS length. The ankyrinG decrease and AIS shortening observed in pharmacologically inhibited neurons and neuron-expressing mDia1 shRNAs were impaired by HDAC6 downregulation or EB1-GFP expression, known to increase microtubule acetylation or stability. However, actin stabilization only partially prevented AIS shortening without affecting AIS protein density loss. These results suggest that mDia1 maintain AIS composition and length contributing to the stability of AIS microtubules.

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Structure and Function of an Actin-Based Filter in the Proximal Axon

Cited by 41 publications

References 29 publications

Role of actin in organelle trafficking in neurons

Role of actin in organelle trafficking in neurons

Tropomyosin Tpm3.1 is required to maintain the structure and function of the axon initial segment

Formin Activity and mDia1 Contribute to Maintain Axon Initial Segment Composition and Structure

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