scholarly journals Brain-derived neurotrophic factor/neurotrophin 3 regulate axon initial segment location and affect neuronal excitability in cultured hippocampal neurons

2017 ◽  
Vol 142 (2) ◽  
pp. 260-271 ◽  
Author(s):  
Yu Guo ◽  
Zi-jun Su ◽  
Yi-kun Chen ◽  
Zhen Chai
Keyword(s):  
Neurotrophic Factor ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Brain Derived Neurotrophic Factor ◽  
Axon Initial Segment ◽  
Neurotrophin 3 ◽  
Cultured Hippocampal Neurons

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 The Palmitoyl Acyltransferase ZDHHC14 Controls Kv1-Family Potassium Channel Clustering at the Axon Initial Segment

2020 ◽  
Author(s):  
Shaun S. Sanders ◽  
Luiselys M. Hernandez ◽  
Heun Soh ◽  
Santi Karnam ◽  
Randall S. Walikonis ◽  
...  
Keyword(s):  
Potassium Channels ◽  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pdz Domain ◽  
Axon Initial Segment ◽  
Type I ◽  
Action Potential Firing ◽  
Potential Firing ◽  
Palmitoyl Acyltransferase

AbstractThe palmitoyl acyltransferase (PAT) ZDHHC14 is highly expressed in the hippocampus and is the only PAT predicted to bind Type I PDZ domain-containing proteins. However, ZDHHC14’s neuronal roles are unknown. Here, we identify the PDZ domain-containing Membrane-associated Guanylate Kinase (MaGUK) PSD93 as a direct ZDHHC14 interactor and substrate. PSD93, but not other MaGUKs, localizes to the Axon Initial Segment (AIS). Using lentiviral-mediated shRNA knockdown in rat hippocampal neurons, we find that ZDHHC14 controls palmitoylation and AIS clustering of PSD93 and also of Kv1 potassium channels, which directly bind PSD93. Neurodevelopmental expression of ZDHHC14 mirrors that of PSD93 and Kv1 channels and, consistent with ZDHHC14’s importance for Kv1 channel clustering, loss of ZDHHC14 decreases outward currents and increases action potential firing in hippocampal neurons. To our knowledge, these findings identify the first neuronal roles and substrates for ZDHHC14 and reveal a previously unappreciated role for palmitoylation in control of neuronal excitability.Impact StatementZDHHC14 controls palmitoylation and axon initial segment targeting of PSD93 and Kv1-family potassium channels, events that are essential for normal neuronal excitability.

scholarly journals The palmitoyl acyltransferase ZDHHC14 controls Kv1-family potassium channel clustering at the axon initial segment

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Shaun S Sanders ◽  
Luiselys M Hernandez ◽  
Heun Soh ◽  
Santi Karnam ◽  
Randall S Walikonis ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Initial Segment ◽  
Neuronal Excitability ◽  
Pdz Domain ◽  
Axon Initial Segment ◽  
Type I ◽  
Action Potential Firing ◽  
Outward Currents ◽  
Potential Firing ◽  
Palmitoyl Acyltransferase

The palmitoyl acyltransferase (PAT) ZDHHC14 is highly expressed in the hippocampus and is the only PAT predicted to bind Type-I PDZ domain-containing proteins. However, ZDHHC14’s neuronal roles are unknown. Here, we identify the PDZ domain-containing Membrane-associated Guanylate Kinase (MaGUK) PSD93 as a direct ZDHHC14 interactor and substrate. PSD93, but not other MaGUKs, localizes to the axon initial segment (AIS). Using lentiviral-mediated shRNA knockdown in rat hippocampal neurons, we find that ZDHHC14 controls palmitoylation and AIS clustering of PSD93 and also of Kv1 potassium channels, which directly bind PSD93. Neurodevelopmental expression of ZDHHC14 mirrors that of PSD93 and Kv1 channels and, consistent with ZDHHC14’s importance for Kv1 channel clustering, loss of ZDHHC14 decreases outward currents and increases action potential firing in hippocampal neurons. To our knowledge, these findings identify the first neuronal roles and substrates for ZDHHC14 and reveal a previously unappreciated role for palmitoylation in control of neuronal excitability.

scholarly journals Brain-Derived Neurotrophic Factor Promotes the Maturation of GABAergic Mechanisms in Cultured Hippocampal Neurons

2002 ◽  
Vol 22 (17) ◽  
pp. 7580-7585 ◽  
Author(s):  
Maki K. Yamada ◽  
Kohsuke Nakanishi ◽  
Shizu Ohba ◽  
Takeshi Nakamura ◽  
Yuji Ikegaya ◽  
...  
Keyword(s):  
Neurotrophic Factor ◽  
Hippocampal Neurons ◽  
Brain Derived Neurotrophic Factor ◽  
Cultured Hippocampal Neurons

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
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