Spatial relationships of utrophin, dystrophin, beta-dystroglycan and beta-spectrin to acetylcholine receptor clusters during postnatal maturation of the rat neuromuscular junction

Guy Smith Bewick, C Young, C R Slater

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Abstract

At the adult mammalian neuromuscular junction, acetylcholine receptors are concentrated at the tops of the postsynaptic folds and voltage-gated sodium channels are concentrated in their depths. It is likely that this arrangement involves linkage of the ion channels to components of the underlying membrane cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises as part of the developmental remodelling of the junctional region during the first few weeks after birth. We have followed the changes during this period in the distribution of four proteins associated with the postsynaptic cytoskeleton at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and beta-spectrin) to see if any of them co-localizes with acetylcholine receptors during the remodelling process, as would be required if it serves to link acetylcholine receptors to the cytoskeleton. Each protein was visualized with specific monoclonal antibodies and its distribution at various stages was compared with that of the acetylcholine receptors, labelled with alpha-bungarotoxin. We also related the changes in distribution of these postsynaptic proteins to the main stages in fold formation and, in the Discussion, to reported observations of the accumulation of voltage gated sodium channels during development. Our results show that utrophin labelling is closely co-localized with that of acetylcholine receptors throughout postnatal maturation. beta-dystroglycan labelling is present at most sites of high acetylcholine receptors density throughout maturation although it often extends beyond the region of highest acetylcholine receptors labelling density. By contrast, dystrophin and beta-spectrin labelling is not consistently concentrated at most neuromuscular junctions until after P7 and P14 respectively.
Original languageEnglish
Pages (from-to)367-379
Number of pages13
JournalJournal of Neurocytology
Volume25
Issue number7
Publication statusPublished - 1 Jul 1996

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Utrophin
Dystroglycans
Spectrin
Dystrophin
Neuromuscular Junction
Cholinergic Receptors
Cytoskeleton
Voltage-Gated Sodium Channels
Bungarotoxins
Proteins
Ion Channels
Monoclonal Antibodies
Parturition

Keywords

  • Age Factors
  • Animals
  • Cytoskeletal Proteins
  • Cytoskeleton
  • Dystroglycans
  • Dystrophin
  • Female
  • Fluorescent Antibody Technique
  • Membrane Glycoproteins
  • Membrane Proteins
  • Muscle, Skeletal
  • Neuromuscular Junction
  • Pregnancy
  • Rats
  • Rats, Wistar
  • Receptors, Cholinergic
  • Spectrin
  • Synaptic Membranes
  • Time Factors
  • Utrophin

Cite this

@article{206eeeac355b4118aceedcfc02168ecf,
title = "Spatial relationships of utrophin, dystrophin, beta-dystroglycan and beta-spectrin to acetylcholine receptor clusters during postnatal maturation of the rat neuromuscular junction",
abstract = "At the adult mammalian neuromuscular junction, acetylcholine receptors are concentrated at the tops of the postsynaptic folds and voltage-gated sodium channels are concentrated in their depths. It is likely that this arrangement involves linkage of the ion channels to components of the underlying membrane cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises as part of the developmental remodelling of the junctional region during the first few weeks after birth. We have followed the changes during this period in the distribution of four proteins associated with the postsynaptic cytoskeleton at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and beta-spectrin) to see if any of them co-localizes with acetylcholine receptors during the remodelling process, as would be required if it serves to link acetylcholine receptors to the cytoskeleton. Each protein was visualized with specific monoclonal antibodies and its distribution at various stages was compared with that of the acetylcholine receptors, labelled with alpha-bungarotoxin. We also related the changes in distribution of these postsynaptic proteins to the main stages in fold formation and, in the Discussion, to reported observations of the accumulation of voltage gated sodium channels during development. Our results show that utrophin labelling is closely co-localized with that of acetylcholine receptors throughout postnatal maturation. beta-dystroglycan labelling is present at most sites of high acetylcholine receptors density throughout maturation although it often extends beyond the region of highest acetylcholine receptors labelling density. By contrast, dystrophin and beta-spectrin labelling is not consistently concentrated at most neuromuscular junctions until after P7 and P14 respectively.",
keywords = "Age Factors, Animals, Cytoskeletal Proteins, Cytoskeleton, Dystroglycans, Dystrophin, Female, Fluorescent Antibody Technique, Membrane Glycoproteins, Membrane Proteins, Muscle, Skeletal, Neuromuscular Junction, Pregnancy, Rats, Rats, Wistar, Receptors, Cholinergic, Spectrin, Synaptic Membranes, Time Factors, Utrophin",
author = "Bewick, {Guy Smith} and C Young and Slater, {C R}",
year = "1996",
month = "7",
day = "1",
language = "English",
volume = "25",
pages = "367--379",
journal = "Journal of Neurocytology",
issn = "0300-4864",
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TY - JOUR

T1 - Spatial relationships of utrophin, dystrophin, beta-dystroglycan and beta-spectrin to acetylcholine receptor clusters during postnatal maturation of the rat neuromuscular junction

AU - Bewick, Guy Smith

AU - Young, C

AU - Slater, C R

PY - 1996/7/1

Y1 - 1996/7/1

N2 - At the adult mammalian neuromuscular junction, acetylcholine receptors are concentrated at the tops of the postsynaptic folds and voltage-gated sodium channels are concentrated in their depths. It is likely that this arrangement involves linkage of the ion channels to components of the underlying membrane cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises as part of the developmental remodelling of the junctional region during the first few weeks after birth. We have followed the changes during this period in the distribution of four proteins associated with the postsynaptic cytoskeleton at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and beta-spectrin) to see if any of them co-localizes with acetylcholine receptors during the remodelling process, as would be required if it serves to link acetylcholine receptors to the cytoskeleton. Each protein was visualized with specific monoclonal antibodies and its distribution at various stages was compared with that of the acetylcholine receptors, labelled with alpha-bungarotoxin. We also related the changes in distribution of these postsynaptic proteins to the main stages in fold formation and, in the Discussion, to reported observations of the accumulation of voltage gated sodium channels during development. Our results show that utrophin labelling is closely co-localized with that of acetylcholine receptors throughout postnatal maturation. beta-dystroglycan labelling is present at most sites of high acetylcholine receptors density throughout maturation although it often extends beyond the region of highest acetylcholine receptors labelling density. By contrast, dystrophin and beta-spectrin labelling is not consistently concentrated at most neuromuscular junctions until after P7 and P14 respectively.

AB - At the adult mammalian neuromuscular junction, acetylcholine receptors are concentrated at the tops of the postsynaptic folds and voltage-gated sodium channels are concentrated in their depths. It is likely that this arrangement involves linkage of the ion channels to components of the underlying membrane cytoskeleton. In rats, the mature distribution of acetylcholine receptors arises as part of the developmental remodelling of the junctional region during the first few weeks after birth. We have followed the changes during this period in the distribution of four proteins associated with the postsynaptic cytoskeleton at mature neuromuscular junctions (utrophin, dystrophin, beta-dystroglycan and beta-spectrin) to see if any of them co-localizes with acetylcholine receptors during the remodelling process, as would be required if it serves to link acetylcholine receptors to the cytoskeleton. Each protein was visualized with specific monoclonal antibodies and its distribution at various stages was compared with that of the acetylcholine receptors, labelled with alpha-bungarotoxin. We also related the changes in distribution of these postsynaptic proteins to the main stages in fold formation and, in the Discussion, to reported observations of the accumulation of voltage gated sodium channels during development. Our results show that utrophin labelling is closely co-localized with that of acetylcholine receptors throughout postnatal maturation. beta-dystroglycan labelling is present at most sites of high acetylcholine receptors density throughout maturation although it often extends beyond the region of highest acetylcholine receptors labelling density. By contrast, dystrophin and beta-spectrin labelling is not consistently concentrated at most neuromuscular junctions until after P7 and P14 respectively.

KW - Age Factors

KW - Animals

KW - Cytoskeletal Proteins

KW - Cytoskeleton

KW - Dystroglycans

KW - Dystrophin

KW - Female

KW - Fluorescent Antibody Technique

KW - Membrane Glycoproteins

KW - Membrane Proteins

KW - Muscle, Skeletal

KW - Neuromuscular Junction

KW - Pregnancy

KW - Rats

KW - Rats, Wistar

KW - Receptors, Cholinergic

KW - Spectrin

KW - Synaptic Membranes

KW - Time Factors

KW - Utrophin

M3 - Article

C2 - 8866238

VL - 25

SP - 367

EP - 379

JO - Journal of Neurocytology

JF - Journal of Neurocytology

SN - 0300-4864

IS - 7

ER -