rapsyn

We have isolated and sequenced cDNA clones for the human 43-kDa acetylcholine receptor-associated protein rapsyn. The cDNA encodes a 412-amino-acid protein that has a predicted molecular mass of 46,330 Da and shows 96% sequence identity ..

The 43 kDa AChR-associated protein rapsyn is required for the clustering of nicotinic acetylcholine receptors (AChRs) at the developing neuromuscular junction, but the functions of other postsynaptic proteins colocalized with the AChR are ..

..The receptor tyrosine kinase MuSK is a component of the agrin receptor, while the cytoplasmic protein rapsyn is necessary for the clustering of AChRs and all other postsynaptic membrane components studied to date...

..cell adhesion molecule (N-CAM) and for an acetylcholine receptor-associated cytoskeletal protein (43K-rapsyn). In contrast, RNAs encoding proteins present throughout the muscle were distributed all along the muscle fiber...

..The Congenital Myasthenic Syndromes are a group of genetically determined heterogeneous disorders, usually recessively inherited. The commonest mutation sites appear to be the acetylcholine receptor epsilon-subunit and rapsyn.

..Analysis of the mutations in the AChR-clustering protein, rapsyn, show diverse causes for defective AChR localization and suggest that the common mutation rapsyn-N88K results in ..

..4) Rapsyn clusters AChR at the endplate, and its defects cause endplate AChR deficiency...

..The defects are mainly mutations in the muscle acetylcholine receptor, or associated proteins rapsyn and Dok-7...

..We previously demonstrated that acetylcholine receptors and rapsyn, the 43-kDa receptor-associated protein at the synapse, are cotargeted to the postsynaptic membrane via the ..

..mutations in proteins such as the acetylcholine receptor, acetylcholinesterase, choline acetyltransferase, rapsyn, MuSK and Na(v)1.4...

b>Rapsyn is a postsynaptic protein required for clustering of nicotinic acetylcholine receptors (nAChRs) at the neuromuscular junction. Here we report the mechanism for posttranslational control of rapsyn protein stability...

..We expressed recombinant AChR subunits with the clustering protein, rapsyn, in human embryonic kidney cells and tested for binding of antibodies by immunofluorescence...

..Because late-onset congenital myasthenic syndromes (CMSs) due to RAPSN or DOK7 mutations may be mistaken for SNMG, we investigated their frequency in a nationwide SNMG cohort...

..In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.

..AChR clusters: laminin-beta2, MuSK, phosphotyrosine-containing proteins, beta-dystroglycan, utrophin, and rapsyn. These components have been implicated to play a role in the differentiation of neuromuscular junctions...

..we report that Wnt3a negatively regulates acetylcholine receptor (AChR) clustering by repressing the expression of Rapsyn, an AChR-associated protein essential for AChR clustering...

..and requires a number of intracellular signal or structural proteins, including AChR-associated scaffold protein Rapsyn. Here, we report a role of nuclear factor kappaB (NF-kappaB), a well known transcription factor involved in a ..

..and express muscle proteins including myosin, desmin, acetylcholine receptor (AChR), C-protein, MyoD, troponin T, rapsyn, and utrophin...

..membranes of neuromuscular junctions (NMJ) and forms complexes with acetylcholine receptors (AChR) and rapsyn. MuSK is activated by agrin, which is released from motoneurons, and induces AChR clustering and subsequent ..

..the acetylcholine receptor (AChR) is specifically clustered in the postsynaptic membrane via interactions with rapsyn and other scaffolding proteins...

..electric organ and vertebrate neuromuscular junctions contain the receptor-associated protein of the synapse (RAPsyn) (previously referred to as the 43K protein), a nonactin, 43,000-Mr peripheral membrane protein associated with ..

..Two critical downstream components of this signaling cascade, Dox-7 and rapsyn, have been identified. However, additional intracellular essential elements remain unknown...

43K rapsyn is a peripheral protein specifically associated with the nicotinic acetylcholine receptor (nAChR) present in the postsynaptic membrane of the neuromuscular junction and of the electrocyte, and is essential for its clustering...

..well known as the molecule that aggregates acetylcholine receptor (AChR) through muscle specific kinase (MuSK) and rapsyn at neuromuscular junctions...

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..receptor (AChR) α subunit followed a similar expression pattern, whereas expression of Dok-7, Lrp4 and rapsyn was comparable between the muscles...

..We show that α-actinin, a protein known to cross-link F-actin, interacts with rapsyn, a scaffold protein essential for neuromuscular junction formation...

..This clustering is dependent on activation of the tyrosine kinase, MuSK, which signals receptor clustering via a rapsyn-dependent mechanism...

..formation require several postsynaptic molecular agents including agrin, the tyrosine kinase receptor MuSK and rapsyn. The agrin or motoneuron dependence of this process continues to be debated while the following steps of axonal ..

..and the extracellular matrix involved in the assembly of the postsynaptic membrane, namely the 43-kDa protein-rapsyn, the dystrophin/utrophin complex, agrin, and others...

The acetylcholine receptor (AChR)-associated protein rapsyn is essential for neuromuscular synapse formation and clustering of AChRs, but its mode of action remains unclear...

..b>Rapsyn plays a central role in directing and clustering nAChR during cellular differentiation and neuromuscular junction ..

..kinase activity to promote clustering of AChRs and MuSK itself with a cytoplasmic, receptor-associated protein, rapsyn. These studies, however, have used soluble forms of agrin, whereas agrin is cell- or matrix-attached in vivo...

..Co-transfection experiments in which alpha- and beta-dystroglycan form a complex with AChR and rapsyn, a peripheral protein required for AChR clustering (Apel, D. A., Roberds, S. L., Campbell, K. P., and Merlie, J. P...

..g. dilute lethal phenotype in mice). We examined the role of myosin Va in the postsynaptic plasticity of the vertebrate neuromuscular junction (NMJ)...

..Acetylcholine receptor clustering is also dependent on the postsynaptic scaffolding protein, rapsyn, which binds to acetylcholine receptors...

..Here we demonstrate that the beta-catenin interacts with rapsyn, a molecule key for AChR clustering...

b>Rapsyn, a cytoplasmic receptor-associated protein, is required for the clustering of acetylcholine receptors (AChRs). Although AChR dynamics have been extensively studied, little is known about the dynamics of rapsyn...

..ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor (AChR), rapsyn, plectin, Na(v)1...

..Here, we show that the AChR-associated protein, rapsyn, interacts with PKA type I in C2C12 and T-REx293 cells as well as in live mouse muscle beneath the neuromuscular ..

..Reduction of antigenic modulation by increasing the expression of the receptor-associated anchor protein, rapsyn, or by functionally monovalent competing IgG4 anti-AChR antibodies was shown to prevent MG disease activity...

The receptor-associated protein of the synapse (rapsyn) is required for anchoring and stabilizing the nicotinic acetylcholine receptor (AChR) in the postsynaptic membrane of the neuromuscular junction (NMJ) during development...

..is regulated by the motoneuron-derived factor, agrin, and requires an intracellular, scaffolding protein called rapsyn. However, it remains unclear where rapsyn binds on the acetylcholine receptor and how their interaction is ..

..receptor (AChR), is clustered and anchored in the postsynaptic membrane of the neuromuscular junction by rapsyn. Previously, we found that overexpression of rapsyn by cDNA transfection protects AChRs in rat muscles from ..

..Duplex quantitative PCR using human beta-globin and murine rapsyn primers assessed the contribution of human cells to each tissue...

..DNA analysis failed to detect mutations in the genes encoding any of the following proteins: AChR subunits, rapsyn, ColQ, ChAT or muscle-specific kinase...

..AChR complexes (aggregated and stabilized by rapsyn) are thus prepatterned independently of neuronal signals in developing myofibers...

..This guides rational therapy and multidisciplinary management, which may be crucial for survival, particularly in pedigrees where previous deaths have occurred in infancy...

..of membranes from reinnervated muscle showed that AMPA receptor subunits GluR1 and GluR2 coimmunoprecipitate with rapsyn, the AChR-anchoring protein at the NMJ...

..overlapping functions: in the juxtamembrane region; a nuclear localisation signal, ezrin/radixin/moesin protein, rapsyn and ERK MAP Kinase binding function, and at the C terminus a regulatory tyrosine governing WW, SH2 and SH3 domain ..

..the underlying mechanism and found that Wnt/beta-catenin signaling negatively regulated AChR clustering by downregulating the expression of Rapsyn, an AChR-associated protein required for formation and stabilization of AChR clusters.

..Genetic analyses for AchR, Rapsyn, Musk and AChE were negative...

..Biochemical analyses show that in muscle cells of adult knock-out α-syn mice, total AChRs and scaffold protein rapsyn are significantly reduced, the 89 kDa and 75 kDa isoforms of tyrosine phosphorylated α-dystrobrevin (α-dbn) 1 (..

..To establish an xenogeneic acute graft-versus-host disease model by engraftment of G-CSF mobilized human mononuclear cells into NOD/SCID mice...

..here three patients with a characteristic phenotype of recessive CMS and presenting mutation in the gene encoding rapsyn (RAPSN). Familial analysis showed that one allelic mutation failed to be detected by direct sequencing...

..This first report of the clinical expression of the complete absence of TPM2 in human indicated that TPM2 expression at the early period of prenatal life plays a major role for normal fetal movements...

..proteins identified to date include the acetylcholine receptor, acetylcholinesterase, choline acetyltransferase, rapsyn, and Na(v)1...

..aggregates was reduced in 4-week postnatal mice that had reduced amounts of the AChR-associated protein, rapsyn, in the postsynaptic membrane (rapsyn(+/-) mice)...

..content, which are enriched in several signalling postsynaptic components, notably AChR, the agrin receptor MuSK, rapsyn and syntrophin...

..by agrin signaling via the muscle specific kinase (MuSK) and requires an intracellular scaffolding protein called rapsyn. In addition to its structural role, rapsyn is also necessary for agrin-induced tyrosine phosphorylation of the ..

..branching, increased motoneuron survival, as well as aberrant distribution of acetylcholinesterase (AChE) and rapsyn. However, clustering of muscle specific kinase (MuSK) proceeded normally in the gamma-null muscles...

..MuSK, rapsyn and RIC-3 are accessory molecules associated with muscle and brain nAChR function...

..Mutations identified to date include (i) muscle nicotinic acetylcholine receptor (AChR) subunits, (ii) rapsyn that anchors and clusters AChRs at the neuromuscular junction, (iii) agrin that is released from the nerve ..

..complex is externalized where it co-localizes with other components of the NMJ including dystroglycan, rapsyn, laminin and MuSK...

..mutations in proteins such as choline acetyltransferase acetylcholinesterase, the acetylcholine receptor, rapsyn, and the voltage-gated sodium channel of the Na(v)1.4 type...

..We achieved this by comparing agrin and rapsyn mutant mice that lack acetylcholine receptor (AChR) clusters...

..No E-box mutation has been reported to date. RAPSN encodes rapsyn, a 43 kDa postsynaptic peripheral membrane protein that clusters the nicotinic acetylcholine receptor at the motor ..

..Here, we focused on the dynamics of rapsyn, a protein required for the clustering and maintenance of acetylcholine receptor (AChR) density at postsynaptic ..

..In a subset of CMS patients, endplate AChR deficiency is caused by mutations in rapsyn, a molecule that plays a critical role in concentrating AChR in the postsynaptic membrane.

..mutation in an AChR subunit; endplate AChR deficiency suggested mutations residing in an AChR subunit or in rapsyn; absence of acetylcholinesterase (AChE) from the endplate predicted mutations in the catalytic or collagen-tailed ..

..Laminin-1 also caused extensive coclustering of rapsyn and phosphotyrosine with AChRs, but none of these clusters were observed in rapsyn -/- myotubes...

..junction requires agrin, a nerve-derived signal; MuSK, a critical component of the agrin receptor in muscle; and rapsyn, a protein that interacts with acetylcholine receptors (AChRs)...

..can be determined for nAChR subunits and for other protein components in Torpedo membrane preparations, such as RAPsyn and Na(+)-K(+)-ATPase alpha and beta subunits...

..g., PSD-95, 43K-rapsyn), suggests targeting and assembly of the NO-signaling pathway at postsynaptic membrane components...

..Specifically, in the absence of ACh receptors, clusters of the receptor-aggregating protein rapsyn form in the extrasynaptic membrane but generally fail to localize to the subsynaptic region...

..aggregates, which colocalized with longitudinally oriented beta-dystroglycan, dystrophin, utrophin, syntrophin, rapsyn, and beta 2-laminin in denervated unstimulated fibers and with the same but transversely oriented proteins in ..

b>Rapsyn, a 43 kDa protein required to cluster nicotinic acetylcholine receptors (AChRs) at the neuromuscular junction, is tightly associated with the postsynaptic membrane via an N-terminal myristoylated site...

..previously reported to bind to AChR (including dystrophin-dystrophin-associated protein (DAP) complex, utrophin, rapsyn, and actin; Mitsui et al. [1996] Biochem. Biophys. Res. Commun...

..e., null mutants for agrin, nerve-derived agrin, rapsyn, and MuSK)...

..The deduced sequence of mouse RAPsyn has 412 amino acids and a molecular mass of 46,392 daltons...

..of synapse formation on motoneuron survival during embryonic development, we counted the number of motoneurons in rapsyn-deficient mice...

..The decrease in AChR concentration is correlated with a decrease of postsynaptic rapsyn, but has less effect on agrin, a neuronally released aggregating factor for AChRs...

..While the postsynaptic scaffolding protein rapsyn is vital for high density AChR aggregation, little is known about the mechanism through which AChRs are ..

..Recently, three different mutations in the RAPSN gene have been identified in four CMS patients with AChR deficiency...

..In 2002, the group of A Engel reported the first cases of CMS with mutations in the gene coding rapsyn, a postsynaptic molecule which stabilizes AChR aggregates at the neuromuscular junction...

..and detected many proteins linked to AChR, including dystrophin, adhalin, beta-dystroglycan, utrophin, rapsyn, and actin...

..Finally, we show that erbB3 is not concentrated at synaptic sites in mutant mice that lack rapsyn, a cytoskeletal protein required for AChR clustering, suggesting that pathways for synaptic AChR expression and ..

..Recent advances have revealed agrin, muscle-specific kinase (MuSK) and rapsyn as important signalling elements in the development and maintainance of the molecular architecture of the ..

..cases of 3 children with postsynaptic congenital myasthenic syndrome with acetylcholine receptor deficiency due to rapsyn deficiency...

..In this article, a strategy that leads to the diagnosis of congenital myasthenic syndromes is presented, and recent advances in the clinical, genetic and molecular aspects of congenital myasthenic syndrome are outlined...

..The AChR-associated protein rapsyn is essential for forming AChR clusters during development...

..receptor subunits and the following proteins known to be associated with the receptor in the somatic cell: rapsyn and the tyrosine kinases c-SRC and FYN...

..nerves entered transplanted muscles derived from mice lacking muscle-specific receptor tyrosine kinase (MuSK) or rapsyn, muscle-specific components required for postsynaptic differentiation...

Mutations in the human gene encoding rapsyn have been linked to a recessive form of postsynaptic congenital myasthenic syndrome due to deficient clustering of acetylcholine receptors at the endplate...

..A cytoplasmic protein, rapsyn, is essential for AChR clustering in muscle...

..is localized at the postsynaptic membrane containing more AChR-anchoring proteins, including S-laminin and rapsyn in aged animals...

b>Rapsyn, a peripheral membrane protein of skeletal muscle, clusters nicotinic acetylcholine receptors (nAChRs) at high density in the postsynaptic membrane...

b>Rapsyn is essential for clustering the acetylcholine receptor at the postsynaptic membrane of the neuromuscular junction...

The 43 kDa receptor-associated protein rapsyn is a myristoylated peripheral protein that plays a central role in nicotinic acetylcholine receptor (AChR) clustering at the neuromuscular junction...

..Recently, we have shown the defect in one mutant line results from a defective rapsyn gene, and we have succeeded in rescuing the behavioral defect in the mutant fish...

..at the NMJ in which the proteoglycan z-agrin is a nerve-derived signal, MuSK is its main receptor, and rapsyn is a critical intracellular effector leading to aggregation of acetylcholine receptors...

..at the NMJ in which the proteoglycan z-agrin is a nerve-derived signal, MuSK is its main receptor, and rapsyn is a critical intracellular effector leading to aggregation of acetylcholine receptors...

..Here we will co-express the major components of the AChE complex including dystroglycan, perlecan, rapsyn, ColQ and AChE to define the necessary components for trafficking ColQ AChE to the cell surface and assembling ..

..We will investigate nAChR expression and clustering in transgenic mutant models that lack agrin, rapsyn or MuSK, all shown to be key factors in clustering at the NMJ...

..Third, because mutations in other synaptic genes (e.g. AChR subunits, rapsyn, MuSK, AChE) also cause CMS, mutations that interfere with the function of Lrp4 selectively in muscle may also be ..

..Third, because mutations in other synaptic genes (e.g. AChR subunits, rapsyn, MuSK, AChE) also cause CMS, mutations that interfere with the function of Lrp4 selectively in muscle may also be ..

..Here we will co-express the major components of the AChE complex including dystroglycan, perlecan, rapsyn, ColQ and AChE to define the necessary components for trafficking ColQ AChE to the cell surface and assembling ..

..in the redistribution of muscle proteins to the postsynaptic site, including the acetylcholine receptor (AChR), rapsyn, ErbBs and MuSK itself...

..in the redistribution of muscle proteins to the postsynaptic site, including the acetylcholine receptor (AChR), rapsyn, ErbBs and MuSK itself...

..We will also elucidate the mechanisms by which Abl mediates receptor clustering, including an investigation of whether Abl activity is partially mediated by Rapsyn, a protein known to directly affect receptor clustering.

..by inducing phosphorylation of the AChR and altering its association with the intracellular scaffolding protein, rapsyn. We have the following specific aims: (1) To define the role of agrin-induced phosphoryation of the beta subunit ..

..There, the prevailing model is that Agrin signals through MuSK to recruit the intracellular linker Rapsyn, which "clusters acetylcholine receptors (AChRs) on the postsynaptic membrane of neuromuscular junctions...

..including sofa potato (acetylcholine receptor delta subunit), relaxed (dihydropyridine receptor), and twitch once (rapsyn)...

My main objective is to determine how rapsyn directs the increase in AChR density at the neuromuscular junction (NMJ). Severe effects on development and health result when the NMJ becomes impaired...

..study is to determine the dynamics and intracellular trafficking of the acetylcholine receptor associated protein, rapsyn. Rapsyn is the only intracellular protein known to bind directly to acetylcholine receptors, and is functionally ..

..experiments will use the unique advantages offered by zebrafish genetics and development to identify the roles of rapsyn, acetylcholine receptor, MuSK and beta-dystroglycan in synapse formation in vivo...

..In dermatomyositis the hypothesis will be tested that the pathologic features of the disease are mediated by a circulating autoantibody...

..Nicotinic acetylcholine receptors (AChR) and rapsyn will be the focus of this proposal...

..last decade the genes encoding six other molecular targets, including the enzyme choline acetyltransferase (CHAT), rapsyn (RAPSN), the voltage-gated muscle sodium channel (SCN4A), the muscle-specific kinase (MUSK), Dok-7 (DOK7) and the ..