Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex

  title={Rapsyn may function as a link between the acetylcholine receptor and the agrin-binding dystrophin-associated glycoprotein complex},
  author={Elizabeth D. Apel and Steven L. Roberds and Kevin P. Campbell and John Paul Merlie},

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The Dystroglycan Complex Is Necessary for Stabilization of Acetylcholine Receptor Clusters at Neuromuscular Junctions and Formation of the Synaptic Basement Membrane

It is shown that myotubes differentiated from dystroglycan−/− embryonic stem cells are responsive to agrin, but produce acetylcholine receptor (AChR) clusters which are two to three times larger in area, about half as dense, and significantly less stable than those on dystoglycan+/+ myot tubes.

Evidence for in situ and in vitro association between beta-dystroglycan and the subsynaptic 43K rapsyn protein. Consequence for acetylcholine receptor clustering at the synapse.

Investigation of the interaction between rapsyn and beta-dystroglycan in Torpedo AChR-rich membranes shows that a rappingyn-binding site is present in the juxtamembranous region of the cytoplasmic tail of beta- dystrogelcan, reinforcing the notion that dystoglycan could be involved in synaptogenesis.

Agrin Regulates Rapsyn Interaction with Surface Acetylcholine Receptors, and This Underlies Cytoskeletal Anchoring and Clustering*

It is proposed that neural agrin controls postsynaptic aggregation of the A ChR by enhancing rapsyn interaction with surface AChRs and inducing cytoskeletal anchoring and that this is an important precursor step for AChR clustering.

Acetylcholine receptors are required for agrin‐induced clustering of postsynaptic proteins

Results show that AChRs and rapsyn are interdependent components of a pre‐assembled protein complex that is required for agrin‐induced clustering of a full set of postsynaptic proteins, thus providing evidence for an active role of AChR in postsyn synaptic assembly.

Interactions of the Rapsyn RING-H2 Domain with Dystroglycan*

A yeast two-hybrid assay is used to test for interactions at the plasma membrane between rapsyn domains and a nAChR β-subunit fragment, the β-dystroglycan cytoplasmic domain, or rapsys domains and results emphasize the modular character of the rapsy structural domains.

Differential targeting of components of the dystrophin complex to the postsynaptic membrane

This study provides the first evidence for a separate targeting of the various components of the dystrophin‐associated protein complex and a step‐by‐step assembly at the postsynaptic membrane.

Dystroglycan overexpression in vivo alters acetylcholine receptor aggregation at the neuromuscular junction.

Overexpressed dystroglycan altered AChR aggregation in a rostral-caudal gradient, consistent with the sequential development of neuromuscular synapses along the embryo, and supports the hypothesis that dystoglycan is not the myotube-associated specificity component, (MASC) a putative coreceptor needed for agrin to activate muscle-specific kinase (MuSK) and signal ACh R aggregation.

Non-neural agrin codistributes with acetylcholine receptors during early differentiation of Torpedo electrocytes.

Agrin, an extracellular matrix protein synthesized by nerves and muscles, is known to promote the clustering of acetylcholine receptors and other synaptic proteins in cultured myotubes, and the existence of more than one agrin receptor is postulated to account for the action of agrin variants at different stages of the differentiation of the postsynaptic membrane in Torpedo electrocytes.

Overexpression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells

The results indicate that rapsyn expression is essential for agrin-induced AChR clustering but that its overexpression inhibits this pathway.

The postsynaptic submembrane machinery at the neuromuscular junction: Requirement for rapsyn and the utrophin/dystrophin-associated complex

The current understanding of the role of the postsynaptic-submembrane machinery involving rapsyn and the utrophin-associated complex at the neuromuscular synapse is reviewed.



Clustering and immobilization of acetylcholine receptors by the 43-kD protein: a possible role for dystrophin-related protein

It is shown that AChRs present on the fibroblast cell surface prior to transfection of 43k are recruited into 43k-rich membrane domains, and cytoskeletal component, dystrophin related protein (DRP) contributed to the development of AChR clusters.

A role for the dystrophin-glycoprotein complex as a transmembrane linker between laminin and actin

The results support a role for the striated muscle dystrophin-glycoprotein complex in linking the actin- based cytoskeleton with the extracellular matrix and suggest that dystophin and dystroglycan may play substantially different functional roles in nonmuscle tissues.

The role of the cytoplasmic domains of individual subunits of the acetylcholine receptor in 43 kDa protein-induced clustering in COS cells

  • X. YuZ. Hall
  • Biology
    The Journal of neuroscience : the official journal of the Society for Neuroscience
  • 1994
Systematic mutational analysis of the long cytoplasmic loops of the alpha and beta subunits showed that most of the loops can be altered without affecting the ability of the AChR to be clustered; in each case, however, one or more sequences could not be tested, because mutation in these regions prevented A ChR assembly.

Mammalian alpha 1- and beta 1-syntrophin bind to the alternative splice- prone region of the dystrophin COOH terminus

A revised model of the domain organization of dystrophin from the view point of protein-protein interactions is proposed, which suggests that the function of syntrophin is tightly linked to the functional diversity among dyStrophin isoforms.

Mutagenesis of the 43-kD postsynaptic protein defines domains involved in plasma membrane targeting and AChR clustering

The results suggest that membrane association and AChR interactions are separable functions of the 43k molecule.