scholarly journals Ankyrin G membrane partners drive the establishment and maintenance of the axon initial segment

2016 ◽  
Author(s):  
Christophe Leterrier ◽  
Nadine Clerc ◽  
Fanny Rueda-Boroni ◽  
Audrey Montersino ◽  
Bénédicte Dargent ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecules ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Development ◽  
Axon Initial Segment ◽  
Membrane Anchor ◽  
Ankyrin G ◽  
Membrane Components ◽  
Cultured Hippocampal Neurons

The axon initial segment (AIS) is a specialized neuronal compartment that plays a key role in neuronal development and excitability. It concentrates multiple ion channels and cell adhesion molecules. The anchoring of these AIS membrane components is known to be highly dependent of the scaffold protein ankyrin G (ankG) but whether ankG membrane partners play a reciprocal role in ankG targeting and stabilization has not been studied yet. In cultured hippocampal neurons and cortical organotypic slices, we found that shRNA-mediated knockdown of ankG membrane partners led to a decrease of ankG concentration and perturbed the AIS formation and maintenance. These perturbations were rescued by expressing an AIS-targeted sodium channel, or a minimal construct containing the ankyrin-binding domain of Nav1.2 and a membrane anchor. We thus demonstrate that a tight and precocious association of ankG to its membrane partners is crucial for the establishment and maintenance of the AIS.

scholarly journals The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment

2011 ◽  
Vol 286 (27) ◽  
pp. 24385-24393 ◽  
Author(s):  
Martin Kriebel ◽  
Jennifer Metzger ◽  
Sabine Trinks ◽  
Deepti Chugh ◽  
Robert J. Harvey ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Cell Adhesion Molecule ◽  
Synapse Formation ◽  
Growth Factor Receptor ◽  
Axon Initial Segment ◽  
Adult Rat ◽  
Receptor Clusters

Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABAA receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.

scholarly journals Developmental Expression of Kv Potassium Channels at the Axon Initial Segment of Cultured Hippocampal Neurons

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48557 ◽  
Author(s):  
Diana Sánchez-Ponce ◽  
Javier DeFelipe ◽  
Juan José Garrido ◽  
Alberto Muñoz
Keyword(s):  
Potassium Channels ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Developmental Expression ◽  
Cultured Hippocampal Neurons

scholarly journals Assembly and Function of the Juxtaparanodal Kv1 Complex in Health and Disease

Life ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 8
Author(s):  
Delphine Pinatel ◽  
Catherine Faivre-Sarrailh
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Initial Segment ◽  
Axon Initial Segment ◽  
Health And Disease ◽  
Low Threshold ◽  
Frequency Of Action Potentials ◽  
And Function ◽  
Spike Initiation

The precise axonal distribution of specific potassium channels is known to secure the shape and frequency of action potentials in myelinated fibers. The low-threshold voltage-gated Kv1 channels located at the axon initial segment have a significant influence on spike initiation and waveform. Their role remains partially understood at the juxtaparanodes where they are trapped under the compact myelin bordering the nodes of Ranvier in physiological conditions. However, the exposure of Kv1 channels in de- or dys-myelinating neuropathy results in alteration of saltatory conduction. Moreover, cell adhesion molecules associated with the Kv1 complex, including Caspr2, Contactin2, and LGI1, are target antigens in autoimmune diseases associated with hyperexcitability such as encephalitis, neuromyotonia, or neuropathic pain. The clustering of Kv1.1/Kv1.2 channels at the axon initial segment and juxtaparanodes is based on interactions with cell adhesion molecules and cytoskeletal linkers. This review will focus on the trafficking and assembly of the axonal Kv1 complex in the peripheral and central nervous system (PNS and CNS), during development, and in health and disease.

scholarly journals Neural cell adhesion molecule promotes accumulation of TGN organelles at sites of neuron-to-neuron contacts

2002 ◽  
Vol 159 (4) ◽  
pp. 649-661 ◽  
Author(s):  
Vladimir Sytnyk ◽  
Iryna Leshchyns'ka ◽  
Markus Delling ◽  
Galina Dityateva ◽  
Alexander Dityatev ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Hippocampal Neurons ◽  
Cell Adhesion Molecule ◽  
Neural Cell Adhesion Molecule ◽  
Neural Cell ◽  
Initial Contact ◽  
Neural Cell Adhesion ◽  
Intracellular Organelles ◽  
Cultured Hippocampal Neurons

Transformation of a contact between axon and dendrite into a synapse is accompanied by accumulation of the synaptic machinery at this site, being delivered in intracellular organelles mainly of TGN origin. Here, we report that in cultured hippocampal neurons, TGN organelles are linked via spectrin to clusters of the neural cell adhesion molecule (NCAM) in the plasma membrane. These complexes are translocated along neurites and trapped at sites of initial neurite-to-neurite contacts within several minutes after initial contact formation. The accumulation of TGN organelles at contacts with NCAM-deficient neurons is reduced when compared with wild-type cells, suggesting that NCAM mediates the anchoring of intracellular organelles in nascent synapses.

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

2021 ◽  
Author(s):  
Wei Zhang ◽  
María Ciorraga ◽  
Pablo Mendez ◽  
Diana Retana ◽  
Norah Boumedine-Guignon ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Initial Segment ◽  
Protein Transport ◽  
Neuronal Excitability ◽  
Brain Slices ◽  
Axon Initial Segment ◽  
Composition And Structure ◽  
The Stability ◽  
Protein Density ◽  
Voltage Gated Ion Channels

AbstractThe 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.

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

2019 ◽  
Author(s):  
Amr Abouelezz ◽  
Holly Stefen ◽  
Mikael Segerstråle ◽  
David Micinski ◽  
Rimante Minkeviciene ◽  
...  
Keyword(s):  
Actin Filaments ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Actin Polymerization ◽  
Firing Frequency ◽  
Axon Initial Segment ◽  
Action Potential Initiation ◽  
Sodium Ion Channels ◽  
And Function ◽  
Filament Network

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.

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
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