Spatial segregation of membrane proteins is a feature of many excitable cells. In skeletal muscle, clusters of acetylcholine receptors (AChRs) and voltage-gated sodium channels (Na(V)1s) occupy distinct domains at the neuromuscular junction (NMJ). We used quantitative immunolabeling of developing rat soleus muscles to study the mechanism of ion channel segregation and Na(V)1 clustering at NMJs. When Na(V)1s can first be detected, at birth, they already occupy a postsynaptic domain that is distinct from that occupied by AChRs. At this time, Na(V)1s are expressed only in a diffuse area that extends 50-100 microm from the immature NMJ. However, in the region of the high-density AChR cluster at NMJ itself, Na(V)1s are actually present in lower density than in the immediately surrounding membrane. These distinctive features of the Na(V)1 distribution at birth are closely correlated with the distribution of ankyrinG immunolabeling. This suggests that an interaction with ankyrinG plays a role in the initial segregation of Na(V)1s from AChRs. Both Na(V)1 and ankyrinG become clustered at the NMJ itself 1-2 weeks after birth, coincident with the formation of postsynaptic folds. Syntrophin immunolabeling codistributes with AChRs and never resembles that for Na(V)1 or ankyrinG. Therefore, syntrophin is unlikely to play an important part in the initial accumulation of Na(V)1 at the NMJ. These findings suggest that the segregation of Na(V)1 from AChRs begins early in NMJ formation and occurs as a result of the physical exclusion of Na(V)1 and ankyrinG from the region of nerve-muscle contact rather than by a process of active clustering.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6742006 | PMC |
http://dx.doi.org/10.1523/JNEUROSCI.23-06-02102.2003 | DOI Listing |
Matrix Biol
January 2025
German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:
The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability.
View Article and Find Full Text PDFDiscov Med
November 2024
Department of Cardiology, The 82nd Group Army Hospital of the Chinese PLA, 071000 Baoding, Hebei, China.
Background: Hypoxia has a major regulatory impact on the electrical activity transmission in the myocardium, and it is involved in the development of tachyarrhythmia disease. Anchor protein G (ankyrin-G, ANK-G) is associated with voltage-gated Na channels (Nav1.5), but its specific role and mechanism have not been fully defined.
View Article and Find Full Text PDFBiochem Biophys Res Commun
November 2021
State Key Laboratory of Membrane Biology, College of Life Sciences, Peking University, Beijing, 100871, China; PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, 100871, China. Electronic address:
Alzheimer's disease (AD) is the most frequent neurodegenerative disease and a common dementia in elderly individuals. Previous studies found a strong correlation between axon initial segment (AIS) defects and AD, but it remains unclear whether AD itself changes the arrangement of AIS components, and the mechanisms by which adaptor proteins and ion channels in the AIS are disturbed in AD are not well understood. With super-resolution structured illumination microscopy (SIM) revealing axonal structures, here we imaged the lattice structure of completely assembled AIS in APP/PS1 neurons.
View Article and Find Full Text PDFCurr Biol
September 2021
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address:
Skeletal muscle contraction depends on activation of clustered acetylcholine receptors (AchRs) and muscle-specific Na channels (Nav1.4). Some Nav1.
View Article and Find Full Text PDFJ Biol Chem
August 2021
The Frick Center for Heart Failure and Arrhythmia, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University, Columbus, Ohio, USA; Department of Internal Medicine/Division of Cardiovascular Medicine, The Ohio State University, Columbus, Ohio, USA. Electronic address:
Cardiovascular disease (CVD) remains the most common cause of adult morbidity and mortality in developed nations. As a result, predisposition for CVD is increasingly important to understand. Ankyrins are intracellular proteins required for the maintenance of membrane domains.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!