The mammalian 43-kD acetylcholine receptor-associated protein (RAPsyn) is expressed in some nonmuscle cells.

Musil, Linda S.; Frail, Donald E.; Merlie, John P.

doi:10.1083/jcb.108.5.1833

Cited by 28 publications

(15 citation statements)

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“…Rapsyn coprecipitates with the receptor and interacts with all the subunits (12,13) and is essential for nAChR clustering in muscle (14). Rapsyn has also been detected in non-muscle cells, including neurons of the ciliary ganglia, fibroblasts, cardiac cells, and Leydig cells (15)(16)(17).…”

Section: Nicotinic Acetylcholine Receptors (Nachrs)mentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Subunits and Associated Proteins inHuman Sperm

Kumar

Meizel

2005

Journal of Biological Chemistry

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We demonstrated previously the involvement of a nicotinic acetylcholine receptor containing an ␣7 subunit in the human sperm acrosome reaction (a modified exocytotic event essential to fertilization). Here we report the presence in human sperm of ␣7, ␣9, ␣3, ␣5, and ␤4 nicotinic acetylcholine 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. The ␣7 subunit appears to exist as a homomer in the posterior post-acrosomal and neck regions of sperm and is probably linked to the cytoskeleton via rapsyn. The ␣3, ␣5, and ␤4 subunits are present in the sperm flagellar mid-piece of sperm and possibly exist as ␣3␣5␤4 and/or ␣3␤4 channels. The ␣9 subunit is present in the sperm mid-piece. We detected the FYN and c-SRC tyrosine kinases in the flagellar mid-piece region. Both co-precipitated only with the nicotinic acetylcholine receptor ␤4 subunit. Immunolocalization with a C-terminal SRC kinase antibody, which recognizes several members of SRC kinase family, detected a SRC kinase co-localized with the ␣7 subunit in the neck region of sperm. Immunoprecipitation studies with that antibody demonstrated that the ␣7 subunit is associated with a SRC kinase. Antagonists of tyrosine phosphorylation inhibited the acetylcholine-initiated acrosome reaction, suggesting the involvement of a SRC kinase in the acrosome reaction.Nicotinic acetylcholine receptors (nAChRs) 1 are ligand-gated cation channels, mainly found in the central and peripheral nervous system neurons and in skeletal muscle. Nine different ␣ subunits (␣2-␣10) and three different ␤ subunits (␤2-␤4) have been described in the nervous system, with all but the ␣8 subunit present in mammals. Most nAChRs are assumed to form a heteropentameric structure, with various combinations of ␣ and ␤ subunits, except the ␣-bungarotoxin-sensitive ␣7, ␣8, and ␣9 subunits may form homomeric channels (1, 2). Functional nAChRs are also expressed in bronchial epithelial cells, endothelial cells, lymphocytes, keratinocytes, cochlear hair cells, and chromaffin cells (3-7).Many proteins have been shown to be functionally associated with the nAChR (8). One such protein is a 43-kDa peripheral membrane protein, rapsyn (8), that is involved in the association of the receptor to the cytoskeleton (9 -11). Rapsyn coprecipitates with the receptor and interacts with all the subunits (12, 13) and is essential for nAChR clustering in muscle (14). Rapsyn has also been detected in non-muscle cells, including neurons of the ciliary ganglia, fibroblasts, cardiac cells, and Leydig cells (15-17).Protein tyrosine phosphorylation plays an important role in the clustering and cytoskeletal anchoring of the receptor at the neuromuscular junction (18,19), and the SRC family of kinases has been reported to be involved in this mechanism (20). The tyrosine kinases c-SRC and FYN associate with the ␣3␤4 receptor in chromaffin cells and are involved in the cholinergic stimulation of catecholamine secretion by those cells (...

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Section: Nicotinic Acetylcholine Receptors (Nachrs)mentioning

confidence: 99%

Nicotinic Acetylcholine Receptor Subunits and Associated Proteins inHuman Sperm

Kumar

Meizel

2005

Journal of Biological Chemistry

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“…One protein that is required for clustering is the 43K protein (Neubig et al 1979;Sobel et al 1977), now also known as rapsyn (receptor associated protein of the synapse; Musil et al 1989). This membrane-associated cytoplasmic protein was isolated by virtue of its tight association with the AChR.…”

Section: Postsynaptic Regulatorsmentioning

confidence: 99%

Development of the neuromuscular junction

2006

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The differentiation of the neuromuscular junction is a multistep process requiring coordinated interactions between nerve terminals and muscle. Although innervation is not needed for muscle production, the formation of nerve-muscle contacts, intramuscular nerve branching, and neuronal survival require reciprocal signals from nerve and muscle to regulate the formation of synapses. Following the production of muscle fibers, clusters of acetylcholine receptors (AChRs) are concentrated in the central regions of the myofibers via a process termed "prepatterning". The postsynaptic protein MuSK is essential for this process activating possibly its own expression, in addition to the expression of AChR. AChR complexes (aggregated and stabilized by rapsyn) are thus prepatterned independently of neuronal signals in developing myofibers. ACh released by branching motor nerves causes AChR-induced postsynaptic potentials and positively regulates the localization and stabilization of developing synaptic contacts. These "active" contact sites may prevent AChRs clustering in non-contacted regions and counteract the establishment of additional contacts. ACh-induced signals also cause the dispersion of non-synaptic AChR clusters and possibly the removal of excess AChR. A further neuronal factor, agrin, stabilizes the accumulation of AChR at synaptic sites. Agrin released from the branching motor nerve may form a structural link specifically to the ACh-activated endplates, thereby enhancing MuSK kinase activity and AChR accumulation and preventing dispersion of postsynaptic specializations. The successful stabilization of prepatterned AChR clusters by agrin and the generation of singly innervated myofibers appear to require AChR-mediated postsynaptic potentials indicating that the differentiation of the nerve terminal proceeds only after postsynaptic specializations have formed.

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“…So far no other function for rapsyn in vivo has been identified, other than at the neuromuscular synapse (Froehner, 1998). There do exist low levels of rapsyn mRNA in heart, kidney, and brain (Musil et al, 1989; Yang et al, 1997); however, there is no evidence of rapsyn protein expression in these tissues. Given that rapsyn expression is largely muscle‐specific, the enhanced neuronal survival and sprouting observed in rapsyn‐deficient muscles can likely be attributed to the previously defined postsynaptic defects brought about by the absence of rapsyn.…”

Section: Discussionmentioning

confidence: 99%