The Molecular Neurobiology of the Acetylcholine Receptor

McCarthy, Michael; Earnest, J. P.; Young, Ellen; Choe, Seunghyon; Stroud, Robert M.

doi:10.1146/annurev.ne.09.030186.002123

Cited by 182 publications

(64 citation statements)

References 122 publications

(172 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…1). AChR from bovine muscle is a good substitute for the exceedingly scarce human muscle AChR because it can be purified in sufficient amounts (34) and is highly homologous to human AChR ( 14,30,37): the bovine y subunit is 92% identical to the human y subunit (30,37). Lines 2, 3, and 4 responded to 5 ,g/ml of FBAChR at least as strongly as to the highest concentration of y pool used (5 ,ug/ml ofeach peptide) whereas the response to FBAChR of line 1, although significant, was consistently lower than the response to the y pool.…”

Section: Resultsmentioning

confidence: 99%

“…4 depicts alignments of the T epitope sequence segments of the -y subunit with the homologous segments of the other known subunits of human muscle AChR and of the y and E subunits of bovine muscle AChR. The bovine E subunit substitutes for the still unknown sequence of the human E subunit ( 14). Some T epitope peptide sequences are highly diverged (e.g., Hy321-355 and Hy 411-430) and it is unlikely that the corresponding T cells cross-react with homologous segments of other AChR subunits.…”

Section: Discussionmentioning

confidence: 99%

“…The AChR is a complex protein, formed in nonneuronal tissue by four homologous subunits (14). Skeletal muscle AChR exists in two forms, whose expression is developmentally regulated (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.

Protti¹,

Manfredi²,

Wu³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

In myasthenia gravis (MG) an autoimmune response against muscle acetylcholine receptor (AChR) occurs. Embryonic muscle AChR contains a y subunit, substituted in adult muscle by a homologous e subunit. Antibodies and CD4 + cells specific for embryonic AChR have been demonstrated in MG patients.We identified sequence segments of the human y subunit forming epitopes recognized by four embryonic AChR-specific CD4' T cell lines, propagated from MG patients' blood by stimulation with synthetic peptides corresponding to the human -y subunit sequence. Each line had an individual epitope repertoire, but two 20-residue sequence regions were recognized by three lines of different HLA haplotype. Most T epitope sequences were highly diverged between the y and the other AChR subunits, confirming the specificity of the T cells for embryonic AChR. These T cells may have been sensitized against AChR expressed by a tissue other than innervated skeletal muscle, possibly the thymus, which expresses an embryonic muscle AChR-like protein, containing a y subunit. Several sequence segments forming T epitopes are similar to regions of microbial and /or mammalian proteins unrelated to the AChR. These findings are consistent with the possibility that T cell cross-reactivity between unrelated proteins ("molecular mimicry"), proposed as a cause of autoimmune responses, is not a rare event. (J. Clin. Invest. 1992Invest. . 90:1558Invest. -1567

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.

Protti¹,

Manfredi²,

Wu³

et al. 1992

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…The nicotinic acetylcholine receptor (AChR)' is composed of multiple subunits responsible for gating ion flow across membranes in response to binding of the neurotransmitter, acetylcholine (1). The actions of AChR antibodies, either experimentally induced or spontaneous, lead to the numerical reduction of available AChR and prevention of neuromuscular junction's ability to transmit signals from nerve fibers to muscle fibers; medically, the outcome is the autoimmune disease, myasthenia gravis (MG) (1)(2)(3)(4).…”

Section: Introductionmentioning

confidence: 99%

Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

Schwimmbeck¹,

Dyrberg²,

Drachman³

et al. 1989

J. Clin. Invest.

132

View full text Add to dashboard Cite

The large majority of patients with the autoimmune disease myasthenia gravis characteristically have detectable antibodies against the acetykcholine receptor (AChR). We used synthetic peptides to identify antibodies in sera of myasthenia gravis patients reactive with the human acetycholine receptor (HuAChR) a-subunit, residues 160-167. Affinity purification of these antibodies, using the HuAChR a-subunit 157-170 peptide immobilized on thiopropyl-Sepharose, yielded IgG antibodies that bound to the native AChR and inhibited the binding of a-bungarotoxin to the receptor. The HuAChR a-subunit 160-167 peptide demonstrated specific immunological crossreactivity with a shared homologous domain on herpes simplex virus glycoprotein D, residues 286-293, by both binding and inhibition studies. Thus, HuAChR a-subunit, residues 160-167, elicits antibodies in myasthenic patients that binds to the native AChR protein and is capable of eliciting a biologic effect. Immunologic cross-reactivity of this "self" epitope with herpes simplex virus suggest that this virus may be associated with the initiation of some cases of myasthenia.

show abstract

“…The venoms of snakes from the Elapidae and Hydrochiidae groups possess a family of compounds which have very pronounced pharmacological activities (Dufton and Hider, 1983;Endo and Tamiya, 1986), These include long (between 65 and 74 residues) and short (between 60 and 62 residues) neurotoxins known to bind specifically and tightly to the a-subunit of the nicotinic acetylcholine receptor (AChR) (Mennier et aL., 1974;Webber and Changeux, 1974;Lee, 1979;Haggerty and Froehner, 1981). AChR plays a central role in postsynaptic neuromuscular transmission by mediating ion flux across the cell membrane in response to binding of acetylcholine (Karlin, 1980;Conti-Tronconi and Raftery, 1982;McCarthy et aL, 1986;Changeux et at, 1984;Hucho, 1986). Phiding of neurotoxin to AChR is very tight (Kd in the range of 10r 11 M) leading to relatively permanent closure of the ion channel and blockage of the action of acetylcholine.…”

mentioning

confidence: 99%

Molecular Recognition of Alpha-Neurotoxins

Atassi¹

1990

View full text Add to dashboard Cite

The Molecular Neurobiology of the Acetylcholine Receptor

Cited by 182 publications

References 122 publications

Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.

Myasthenia gravis. CD4+ T epitopes on the embryonic gamma subunit of human muscle acetylcholine receptor.

Molecular mimicry and myasthenia gravis. An autoantigenic site of the acetylcholine receptor alpha-subunit that has biologic activity and reacts immunochemically with herpes simplex virus.

Molecular Recognition of Alpha-Neurotoxins

Contact Info

Product

Resources

About