scholarly journals Nanoscale architecture of the axon initial segment reveals an organized and robust scaffold

2015 ◽  
Author(s):  
Christophe Leterrier ◽  
Jean Potier ◽  
Ghislaine Caillol ◽  
Claire Debarnot ◽  
Fanny Rueda Boroni ◽  
...  
Keyword(s):  
Action Potentials ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Molecular Architecture ◽  
Physiological Functions ◽  
Structural Stabilization ◽  
Ankyrin G ◽  
Stochastic Optical Reconstruction Microscopy ◽  
Optical Reconstruction ◽  
Actin Rings

The Axon Initial Segment [AIS], located within the first 30 μm of the axon, has two essential roles in generating action potentials and maintaining axonal identity. AIS assembly depends on a βIV-spectrin / ankyrin G scaffold, but its macromolecular arrangement is not well understood. Here we quantitatively determined the AIS nanoscale architecture using STochastic Optical Reconstruction Microscopy [STORM]. First we directly demonstrate that the 190-nm periodicity of the AIS submembrane lattice results from longitudinal, head-to-head βIV-spectrin molecules connecting actin rings. Using multicolor 3D-STORM, we resolve the nanoscale organization of ankyrin G: its aminoterminus associates with the submembrane lattice, whereas the carboxyterminus radially extends (~32 nm on average) toward the cytosol. This AIS nano-architecture is highly resistant to cytoskeletal perturbations, advocating its role in structural stabilization. Our findings provide a comprehensive view of the AIS molecular architecture, and will help understanding the crucial physiological functions of this compartment.

scholarly journals Ankyrin-G induces nucleoporin Nup358 to associate with the axon initial segment of neurons

2019 ◽  
Vol 132 (18) ◽  
pp. jcs222802 ◽  
Author(s):  
Bouchra Khalaf ◽  
Alessandro Roncador ◽  
Francesca Pischedda ◽  
Antonio Casini ◽  
Sabine Thomas ◽  
...  
Keyword(s):  
Initial Segment ◽  
Axon Initial Segment ◽  
Ankyrin G

scholarly journals Requirement of subunit co-assembly and ankyrin-G for M-channel localization at the axon initial segment

2007 ◽  
Vol 120 (6) ◽  
pp. 953-963 ◽  
Author(s):  
H. B. Rasmussen ◽  
C. Frokjaer-Jensen ◽  
C. S. Jensen ◽  
H. S. Jensen ◽  
N. K. Jorgensen ◽  
...  
Keyword(s):  
Initial Segment ◽  
Axon Initial Segment ◽  
Ankyrin G

scholarly journals Organization of the axon initial segment: Actin like a fence

2016 ◽  
Vol 215 (1) ◽  
pp. 9-11 ◽  
Author(s):  
Yu-Mei Huang ◽  
Matthew N. Rasband
Keyword(s):  
Particle Tracking ◽  
Single Particle ◽  
High Speed ◽  
Initial Segment ◽  
Single Particle Tracking ◽  
Axon Initial Segment ◽  
Membrane Domains ◽  
Superresolution Microscopy ◽  
Cell Biol ◽  
Actin Rings

What prevents the movement of membrane molecules between axonal and somatodendritic domains is unclear. In this issue, Albrecht et. al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603108) demonstrate via high-speed single-particle tracking and superresolution microscopy that lipid-anchored molecules in the axon initial segment are confined to membrane domains separated by periodically spaced actin rings.

scholarly journals Contribution of the axon initial segment to action potentials recorded extracellularly

2018 ◽  
Author(s):  
Maria Teleńczuk ◽  
Romain Brette ◽  
Alain Destexhe ◽  
Bartosz Teleńczuk
Keyword(s):  
Action Potential ◽  
Electric Fields ◽  
Action Potentials ◽  
Initial Segment ◽  
Initiation Site ◽  
Axon Initial Segment ◽  
Neuron Activity ◽  
Classical Models ◽  
The Brain

AbstractAction potentials (APs) are electric phenomena that are recorded both intracellularly and extracellularly. APs are usually initiated in the short segment of the axon called the axon initial segment (AIS). It was recently proposed that at onset of an AP the soma and the AIS form a dipole. We study the extracellular signature (the extracellular action potential, EAP) generated by such a dipole. First, we demonstrate the formation of the dipole and its extracellular signature in detailed morphological models of a reconstructed pyramidal neuron. Then, we study the EAP waveform and its spatial dependence in models with axonal AP initiation and contrast it with the EAP obtained in models with somatic AP initiation. We show that in the models with axonal AP initiation the dipole forms between somatodendritic compartments and the AIS, and not between soma and dendrites as in the classical models. Soma-dendrites dipole is present only in models with somatic AP initiation. Our study has consequences for interpreting extracellular recordings of single-neuron activity and determining electrophysiological neuron types, but also for better understanding the origins of the high-frequency macroscopic electric fields recorded in the brain.New & NoteworthyWe studied the consequences of the action potential (AP) initiation site on the extracellular signatures of APs. We show that: (1) at the time of AP initiation the action initial segment (AIS) forms a dipole with the soma, (2) the width but not (3) amplitude of the extracellular AP generated by this dipole increases with the soma-AIS distance. This may help to monitor dynamic changes in the AIS position in experimental in vivo recordings.

Sub-membranous actin rings in the axon initial segment are resistant to the action of latrunculin

2019 ◽  
Vol 400 (9) ◽  
pp. 1141-1146 ◽  
Author(s):  
Amr Abouelezz ◽  
David Micinski ◽  
Aino Lipponen ◽  
Pirta Hotulainen
Keyword(s):  
Actin Cytoskeleton ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Dependent Manner ◽  
Latrunculin A ◽  
Actin Rings ◽  
Dose Dependent

Abstract The axon initial segment (AIS) comprises a sub-membranous lattice containing periodic actin rings. The overall AIS structure is insensitive to actin-disrupting drugs, but the effects of actin-disrupting drugs on actin rings lack consensus. We examined the effect of latrunculin A and B on the actin cytoskeleton of neurons in culture and actin rings in the AIS. Both latrunculin A and B markedly reduced the overall amount of F-actin in treated neurons in a dose-dependent manner, but the periodicity of actin rings remained unaffected. The insensitivity of AIS actin rings to latrunculin suggests they are relatively stable.

scholarly journals NuMA1 promotes axon initial segment assembly through inhibition of endocytosis

2019 ◽  
pp. jcb.201907048 ◽  
Author(s):  
Tomohiro Torii ◽  
Yuki Ogawa ◽  
Cheng-Hsin Liu ◽  
Tammy Szu-Yu Ho ◽  
Hamdan Hamdan ◽  
...  
Keyword(s):  
Transient Expression ◽  
Action Potentials ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Neonatal Mouse ◽  
Scaffolding Protein ◽  
Differential Proteomics ◽  
Mitotic Apparatus ◽  
Axon Initial Segments ◽  
Protein 4.1B

Axon initial segments (AISs) initiate action potentials and regulate the trafficking of vesicles between somatodendritic and axonal compartments. However, the mechanisms controlling AIS assembly remain poorly defined. We performed differential proteomics and found nuclear mitotic apparatus protein 1 (NuMA1) is downregulated in AIS-deficient neonatal mouse brains and neurons. NuMA1 is transiently located at the AIS during development where it interacts with the scaffolding protein 4.1B and the dynein regulator lissencephaly 1 (Lis1). Silencing NuMA1 or protein 4.1B by shRNA disrupts AIS assembly, but not maintenance. Silencing Lis1 or overexpressing NuMA1 during AIS assembly increased the density of AIS proteins, including ankyrinG and neurofascin-186 (NF186). NuMA1 inhibits the endocytosis of AIS NF186 by impeding Lis1’s interaction with doublecortin, a potent facilitator of NF186 endocytosis. Our results indicate the transient expression and AIS localization of NuMA1 stabilizes the developing AIS by inhibiting endocytosis and removal of AIS proteins.

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