Chapter 12 Regulation of Membrane Protein Organization at the Neuromuscular Junction

Publisher Summary This chapter discusses the regulation of membrane-protein organization at the neuromuscular junction. Agrin is an extracellular-matrix protein released by the motor neuron at the time of synapse formation. It resides in the synaptic cleft of the neuromuscular junction (NMJ), where it forms part of the stable basal lamina. In this location, agrin induces the formation of Ach receptor (AchR) clusters under the nerve-muscle synapse. The underlying molecular mechanisms of agrin's actions are likely to involve tethering AChR to the cytoskeleton. Several lines of evidence support this hypothesis. First, agrin induces cluster formation by redistributing AChR already present on the muscle-cell membrane and has no effect on AchR-subunit synthesis. Second, AChR clusters are more resistant to detergent extraction than unclustered receptors. Third, many spectrin-like molecules, including syntrophin, utrophin, p-spectrin, the 87-kDa protein, and rapsyn, are specifically co-localized with AChRs at the NMJ. These molecules are likely to serve as a link between AChRs and the actin cytoskeleton. Agrin binds to α-dystroglycan (DG), a glycoprotein complex (GC) member. The GC is linked to the cytoskeleton by binding dystrophin or utrophin, spectrin-like proteins known to bind F-actin. These data provide a model in which agrin, by binding to a-DG, traps the AChRs as they diffuse into the agrin-receptorcytoskeleton complex.

• Publication year

  1996

• Venue

  Current Topics in Membranes

• Publication date

  Unknown publication date

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/S0070-2161(08)60392-5
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Neuregulins are concentrated at nerve-muscle synapses and activate ACh–receptor gene expression

  1995cited by this paper
• Three muscular dystrophies: loss of cytoskeleton-extracellular matrix linkage.

  1995cited by this paper
• Agrin Is a Heparan Sulfate Proteoglycan (*)

  1995cited by this paper
• SH3 Domain-mediated Interaction of Dystroglycan and Grb2(*)

  1995cited by this paper
• Assembly of the postsynaptic apparatus.

  1995cited by this paper
• Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex.

  1995cited by this paper
• Identification of α-Syntrophin Binding to Syntrophin Triplet, Dystrophin, and Utrophin (*)

  1995cited by this paper
• Syntrophin binds to an alternatively spliced exon of dystrophin

  1995cited by this paper
• Utrophin actin binding domain: analysis of actin binding and cellular targeting.

  1995cited by this paper
• Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice- prone region of the dystrophin COOH terminus

  1995cited by this paper
• A motoneuron-selective stop signal in the synaptic protein S-laminin.

  1995cited by this paper
• Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury.

  1995cited by this paper
• Acetylcholine receptor aggregation at nerve-muscle contacts in mammalian cultures: induction by ventral spinal cord neurons is specific to axons

  1995cited by this paper
• Dystrophin-glycoprotein complex: molecular organization and critical roles in skeletal muscle.

  1995cited by this paper
• Regulation of the interaction of nicotinic acetylcholine receptors with the cytoskeleton by agrin-activated protein tyrosine kinase

  1995cited by this paper
• Distribution of alpha-dystroglycan during embryonic nerve-muscle synaptogenesis

  1995cited by this paper
• Role for a synapse-specific carbohydrate in agrin-induced clustering of acetylcholine receptors.

  1995cited by this paper
• Acetylcholine receptor-aggregating activity of agrin isoforms and mapping of the active site

  1995cited by this paper
• Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice

  1995cited by this paper
• Follistatin, an antagonist of activin, is expressed in the Spemann organizer and displays direct neuralizing activity.

  1994cited by this paper
• Heterogeneity of the 59-kDa dystrophin-associated protein revealed by cDNA cloning and expression.

  1994cited by this paper
• The role of the cytoplasmic domains of individual subunits of the acetylcholine receptor in 43 kDa protein-induced clustering in COS cells

  1994cited by this paper
• Increasing complexity of the dystrophin-associated protein complex.

  1994cited by this paper
• Staurosporine inhibits agrin-induced acetylcholine receptor phosphorylation and aggregation

  1994cited by this paper
• Localization and alternative splicing of agrin mRNA in adult rat brain: transcripts encoding isoforms that aggregate acetylcholine receptors are not restricted to cholinergic regions

  1994cited by this paper
• Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24.

  1994cited by this paper
• Structural domains of agrin required for clustering of nicotinic acetylcholine receptors.

  1994cited by this paper
• A role for dystrophin-associated glycoproteins and utrophin in agrin-induced AChR clustering.

  1994cited by this paper
• Inhibition of activin receptor signaling promotes neuralization in Xenopus.

  1994cited by this paper
• Molecular organization at the glycoprotein-complex-binding site of dystrophin. Three dystrophin-associated proteins bind directly to the carboxy-terminal portion of dystrophin.

  1994cited by this paper
• Dystroglycan binds nerve and muscle agrin.

  1994cited by this paper
• beta 2-Syntrophin: localization at the neuromuscular junction in skeletal muscle.

  1994cited by this paper
• Tyrosine and Serine Phosphorylation of Dystrophin and the 58‐kDa Protein in the Postsynaptic Membrane of Torpedo Electric Organ

  1994cited by this paper
• Association of utrophin and multiple dystrophin short forms with the mammalian M(r) 58,000 dystrophin-associated protein (syntrophin).

  1994cited by this paper
• Dystroglycan-α, a dystrophin-associated glycoprotein, is a functional agrin receptor

  1994cited by this paper
• Dystrophin-associated proteins and synapse formation: Is α-dystroglycan the agrin receptor?

  1994cited by this paper
• Identification and purification of an agrin receptor from Torpedo postsynaptic membranes: a heteromeric complex related to the dystroglycans.

  1994cited by this paper
• Two forms of mouse syntrophin, a 58 kd dystrophin-associated protein, differ in primary structure and tissue distribution.

  1993cited by this paper
• The 87K postsynaptic membrane protein from Torpedo is a protein-tyrosine kinase substrate homologous to dystrophin.

  1993cited by this paper
• Clustering and immobilization of acetylcholine receptors by the 43-kD protein: a possible role for dystrophin-related protein

  1993cited by this paper
• The role of p21ras in receptor tyrosine kinase signaling.

  1993cited by this paper
• ARIA, a protein that stimulates acetylcholine receptor synthesis, is a member of the neu ligand family.

  1993cited by this paper
• A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin

  1993cited by this paper
• Dystrophin and the membrane skeleton.

  1993cited by this paper
• Developmental expression and alternative splicing of chick agrin RNA.

  1993cited by this paper
• Developmental regulation of highly active alternatively spliced forms of agrin.

  1993cited by this paper
• Agrin and the molecular choreography of synapse formation.

  1993cited by this paper
• Development of the neuromuscular synapse.

  1993cited by this paper
• The agrin receptor. Localization in the postsynaptic membrane, interaction with agrin, and relationship to the acetylcholine receptor.

  1993cited by this paper
• 43K protein and acetylcholine receptors colocalize during the initial stages of neuromuscular synapse formation in vivo.

  1993cited by this paper
• Interaction of the 43 kd postsynaptic protein with all subunits of the muscle nicotinic acetylcholine receptor.

  1993cited by this paper
• The ability of agrin to cluster AChRs depends on alternative splicing and on cell surface proteoglycans.

  1993cited by this paper
• Synaptic structure and development: the neuromuscular junction.

  1993cited by this paper
• Molecular cloning of two abundant protein tyrosine kinases in Torpedo electric organ that associate with the acetylcholine receptor.

  1993cited by this paper
• Localization of dystrophin and beta-spectrin in vacuolar myopathies.

  1993cited by this paper
• Proteins associated with the cytoplasmic surface of adhesion molecules.

  1993cited by this paper
• Functions of agrin and agrin-related proteins.

  1993cited by this paper
• The agrin gene codes for a family of basal lamina proteins that differ in function and distribution.

  1992cited by this paper
• Expression of the N‐terminal domain of dystrophin in E. coli and demonstration of binding to F‐actin

  1992cited by this paper
• The subcellular distribution of chromosome 6-encoded dystrophin-related protein in the brain

  1992cited by this paper
• Different distributions of dystrophin and related proteins at nerve-muscle junctions.

  1992cited by this paper
• Association of the Mr 58,000 postsynaptic protein of electric tissue with Torpedo dystrophin and the Mr 87,000 postsynaptic protein.

  1992cited by this paper
• RNA splicing regulates agrin-mediated acetylcholine receptor clustering activity on cultured myotubes.

  1992cited by this paper
• Agrin released by motor neurons induces the aggregation of acetylcholine receptors at neuromuscular junctions.

  1992cited by this paper
• Association of dystrophin-related protein with dystrophin-associated proteins in mdx mouse muscle

  1992cited by this paper
• cDNA that encodes active agrin.

  1992cited by this paper
• The reverse transcriptase of hepatitis B virus acts as a protein primer for viral DNA synthesis.

  1992cited by this paper
• Binding sites involved in the interaction of actin with the N‐terminal region of dystrophin

  1992cited by this paper
• Analysis of the actin-binding domain of alpha-actinin by mutagenesis and demonstration that dystrophin contains a functionally homologous domain

  1992cited by this paper
• Neurexins: synaptic cell surface proteins related to the alpha-latrotoxin receptor and laminin.

  1992cited by this paper
• Structure and expression of the membrane proteoglycan betaglycan, a component of the TGF-beta receptor system.

  1991cited by this paper
• The subcellular distribution of dystrophin in mouse skeletal, cardiac, and smooth muscle

  1991cited by this paper
• Cytoplasmic components of acetylcholine receptor clusters of cultured rat myotubes: the 58-kD protein

  1991cited by this paper
• The mechanism of agrin-induced acetylcholine receptor aggregation.

  1991cited by this paper
• Agrin mediates cell contact-induced acetylcholine receptor clustering.

  1991cited by this paper
• Requirement of heparan sulfate for bFGF-mediated fibroblast growth and myoblast differentiation

  1991cited by this paper
• The submembrane machinery for nicotinic acetylcholine receptor clustering

  1991cited by this paper
• Agrin induces phosphorylation of the nicotinic acetylcholine receptor.

  1991cited by this paper
• Glycosaminoglycans: molecular properties, protein interactions, and role in physiological processes.

  1991cited by this paper
• Structure and expression of a rat agrin.

  1991cited by this paper
• Dystrophin-related protein is localized to neuromuscular junctions of adult skeletal muscle.

  1991cited by this paper
• Cell surface, heparin-like molecules are required for binding of basic fibroblast growth factor to its high affinity receptor.

  1991cited by this paper
• ACh receptor-rich membrane domains organized in fibroblasts by recombinant 43-kildalton protein

  1991cited by this paper
• Comparison of agrin-like proteins from the extracellular matrix of chicken kidney and muscle with neural agrin, a synapse organizing protein.

  1991cited by this paper
• Localization of dystrophin relative to acetylcholine receptor domains in electric tissue and adult and cultured skeletal muscle

  1991cited by this paper
• Synthesis and transport of agrin-like molecules in motor neurons.

  1990cited by this paper
• Molecular heterogeneity of basal laminae: isoforms of laminin and collagen IV at the neuromuscular junction and elsewhere

  1990cited by this paper
• The postsynaptic 43K protein clusters muscle nicotinic acetylcholine receptors in Xenopus oocytes.

  1990cited by this paper
• Strategic location of calcium channels at transmitter release sites of frog neuromuscular synapses.

  1990cited by this paper
• Agrin-like molecules in motor neurons.

  1990cited by this paper
• The agrin hypothesis.

  1990cited by this paper
• The many faces of epidermal growth factor repeats.

  1990cited by this paper
• Spectrin-based membrane skeleton: a multipotential adaptor between plasma membrane and cytoplasm.

  1990cited by this paper
• Inhibition of agrin-induced acetylcholine-receptor aggregation by heparin, heparan sulfate, and other polyanions

  1990cited by this paper
• An unusual beta-spectrin associated with clustered acetylcholine receptors

  1989cited by this paper
• Laminin A chain synthetic peptide which supports neurite outgrowth.

  1989cited by this paper
• A laminin-like adhesive protein concentrated in the synaptic cleft of the neuromuscular junction

  1989cited by this paper
• Domains of laminin with growth-factor activity.

  1989cited by this paper
• Agrin-induced specializations contain cytoplasmic, membrane, and extracellular matrix-associated components of the postsynaptic apparatus

  1989cited by this paper
• Distribution of Na+ channels and ankyrin in neuromuscular junctions is complementary to that of acetylcholine receptors and the 43 kd protein.

  1989cited by this paper

• Activation of neurospecific gene expression by antennapedia homeobox peptide

  2000cites this paper