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

Apel, Elizabeth D.; Roberds, Steven L.; Campbell, Kevin P.; Merlie, John P.

doi:10.1016/0896-6273(95)90069-1

Cited by 197 publications

(115 citation statements)

References 63 publications

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“…The ability of syntrophin to link NaChs to dystrophin and the DAPC is reminiscent of the AChRassociated protein rapsyn. Cotransfection experiments have demonstrated that rapsyn can cluster AChRs (Froehner et al, 1990;Phillips et al, 1991;Apel et al, 1995) and ␣-and ␤-dystroglycan (Apel et al, 1995(Apel et al, , 1997, extracellular and transmembrane proteins, respectively, of the DAPC (Ervasti and C ampbell, 1991). Thus, rapsyn may f unction as a link between AChRs and the DAPC.…”

Section: Discussionmentioning

confidence: 99%

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

et al. 1998

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Syntrophins are cytoplasmic peripheral membrane proteins of the dystrophin-associated protein complex (DAPC). Three syntrophin isoforms, ␣1, ␤1, and ␤2, are encoded by distinct genes. Each contains two pleckstrin homology (PH) domains, a syntrophin-unique (SU) domain, and a PDZ domain. The name PDZ comes from the first three proteins found to contain repeats of this domain (PSD-95, Drosophila discs large protein, and the zona occludens protein 1). PDZ domains in other proteins bind to the C termini of ion channels and neurotransmitter receptors containing the consensus sequence (S/T)XV-COOH and mediate the clustering or synaptic localization of these proteins. Two voltage-gated sodium channels (NaChs), SkM1 and SkM2, of skeletal and cardiac muscle, respectively, have this consensus sequence. Because NaChs are sarcolemmal components like syntrophins, we have investigated possible interactions between these proteins. NaChs copurify with syntrophin and dystrophin from extracts of skeletal and cardiac muscle. Peptides corresponding to the C-terminal 10 amino acids of SkM1 and SkM2 are sufficient to bind detergentsolubilized muscle syntrophins, to inhibit the binding of native NaChs to syntrophin PDZ domain fusion proteins, and to bind specifically to PDZ domains from ␣1-, ␤1-, and ␤2-syntrophin. These peptides also inhibit binding of the syntrophin PDZ domain to the PDZ domain of neuronal nitric oxide synthase, an interaction that is not mediated by C-terminal sequences. Brain NaChs, which lack the (S/T)XV consensus sequence, also copurify with syntrophin and dystrophin, an interaction that does not appear to be mediated by the PDZ domain of syntrophin. Collectively, our data suggest that syntrophins link NaChs to the actin cytoskeleton and the extracellular matrix via dystrophin and the DAPC.

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Section: Discussionmentioning

confidence: 99%

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

et al. 1998

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“…The finding that AChRs are linked to the DGC via rapsyn ( Fig. 2; Apel et al 1995), an intracellular protein exclusively found at the NMJ, suggests that the binding of agrin to a-dystroglycan may be a way of indirectly attaching AChRs and perhaps additional post-synaptic components to the synaptic region of the basal lamina of the muscle fiber. In conclusion, agrin may have a structural function at the NMJ, in addition to its role in the induction of synaptic differentiation.…”

Section: A Potential Role Of Agrin In the Stabilization Of Junctionalmentioning

confidence: 99%

Synaptic differentiation: the role of agrin in the formation and maintenance of the neuromuscular junction

Denzer

Hauser

Gesemann

et al. 1997

Cell and Tissue Research

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Abstract. Upon arrival of a motor axon at the muscle fiber, signals released from its growth cone initiate the formation of a synapse. This process consists of two stages: arrest of axon growth at the target area and differentiation of pre-and postsynaptic cells at the site of nerve-muscle contact. Studies of regenerating neuromuscular junctions in vertebrates have revealed that important signals for the formation of this synapse are located in the synaptic basal lamina, and attempts to identify these signals have led to the isolation of agrin and other components. In this review, we discuss the evidence for the involvement of these molecules and their potential functional role in the formation and maintenance of the neuromuscular junction, with emphasis on agrin.

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“…Rapsyn is believed to bridge the receptor to cytoskeletal proteins (Apel et al, 1995). There is a consensus myristoylation site in the N terminal of the rapsyn protein.…”

Section: Regulation Of the Interaction Between The Achr And Rapsyn Bymentioning

confidence: 99%

Lipid Rafts Serve as a Signaling Platform for Nicotinic Acetylcholine Receptor Clustering

Zhu¹,

Xiong²,

Mei³

2006

J. Neurosci.

130

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Agrin, a motoneuron-derived factor, and the muscle-specific receptor tyrosine kinase (MuSK) are essential for the acetylcholine receptor (AChR) clustering at the postjunctional membrane. However, the underlying signaling mechanisms remain poorly defined. We show that agrin stimulates a dynamic translocation of the AChR into lipid rafts-cholesterol and sphingolipid-rich microdomains in the plasma membrane. This follows MuSK partition into lipid rafts and requires its activation. Disruption of lipid rafts inhibits MuSK activation and downstream signaling and AChR clustering in response to agrin. Rapsyn, an intracellular protein necessary for AChR clustering, is located constitutively in lipid rafts, but its interaction with the AChR is inhibited when lipid rafts are perturbed. These results reveal that lipid rafts may regulate AChR clustering by facilitating the agrin/MuSK signaling and the interaction between the receptor and rapsyn, both necessary for AChR clustering and maintenance. These results provide insight into mechanisms of AChR cluster formation.

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

Cited by 197 publications

References 63 publications

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

Interaction of Muscle and Brain Sodium Channels with Multiple Members of the Syntrophin Family of Dystrophin-Associated Proteins

Synaptic differentiation: the role of agrin in the formation and maintenance of the neuromuscular junction

Lipid Rafts Serve as a Signaling Platform for Nicotinic Acetylcholine Receptor Clustering

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