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Gene Review

Rapsn  -  receptor-associated protein of the synapse

Mus musculus

Synonyms: 43 kDa postsynaptic protein, 43 kDa receptor-associated protein of the synapse, 43kDa, 43kDa acetylcholine receptor-associated protein, Acetylcholine receptor-associated 43 kDa protein, ...
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Disease relevance of Rapsn


High impact information on Rapsn

  • We report that the initial steps in postsynaptic differentiation and formation of an end-plate band require MuSK and rapsyn, but are not dependent on agrin or the presence of motor axons [2].
  • Much evidence suggests that the nerve-derived protein agrin activates muscle-specific kinase (MuSK) to cluster AChRs through the synapse-specific cytoplasmic protein rapsyn [2].
  • Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice [3].
  • 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 [4].
  • We conclude that the expression of RAPsyn and the acetylcholine receptor is not coordinately regulated in mouse muscle [5].

Biological context of Rapsn

  • Finally, the 43K locus, designated Rapsn, has been mapped to the central region of mouse chromosome 2 [6].
  • However, the phenotypes of these mutants differed in several respects, suggesting that the pathway from agrin to MuSK to rapsyn is complex [7].
  • Finally, genomic DNA blot analysis indicates that a single N-RAPsyn gene is present in the mouse genome [8].
  • Rapsyn-EGFP also targeted directly to the postsynaptic membrane where it occupied previously vacant rapsyn binding sites, thereby increasing the rapsyn to AChR ratio [9].
  • To evaluate the role of synapse formation on motoneuron survival during embryonic development, we counted the number of motoneurons in rapsyn-deficient mice [10].

Anatomical context of Rapsn

  • Rapsyn is a synapse-specific protein that is required for clustering acetylcholine receptors at the neuromuscular junction [11].
  • Agrin acts by activating the muscle-specific kinase MuSK and inducing coaggregation of the 43-kDa protein rapsyn with AChRs on muscle cell membrane [12].
  • RAPsyn synthesized in both muscle and nonmuscle cells was shown to be tightly associated with membranes [13].
  • Analysis of these immunoprecipitates by SDS-PAGE revealed detectable RAPsyn synthesis in some (notably fibroblast and Leydig tumor cell lines and primary cardiac cells) but not all (hepatocyte- and lymphocyte-derived) cell types [13].
  • Torpedo 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 the cytoplasmic face of postsynaptic membranes at areas of high nicotinic acetylcholine receptor (AChR) density [13].

Associations of Rapsn with chemical compounds

  • Characterization and mapping of the Rapsn gene encoding the 43-kDa acetylcholine receptor-associated protein [6].
  • The RAPsyn protein present in undifferentiated and differentiated muscle cells cannot be distinguished by peptide maps, turnover rates, cellular subfractionation, or ability to incorporate myristate [5].
  • The overall identity with Torpedo RAPsyn is 70%; some regions are extremely well conserved and are therefore postulated to be functionally important [8].
  • After treatment with various agrin constructs containing the full C-terminally AChR-clustering domain (fragments N2, N4), but not with fragment C2 (truncated), NOS-1 expressed in the cytosol of mouse C2C12 skeletal myotubes coclustered with AChR, 43K rapsyn, MuSK, and the dystrophin/utrophin glycoprotein-complex (DUGC) [14].
  • Substitution mutation to the C-terminal serine phosphorylation site of rapsyn (M43(D405,D406)) did not impair the response to agrin, showing that differential phosphorylation of this site is unlikely to mediate agrin-induced clustering [15].

Physical interactions of Rapsn

  • Dystroglycan is necessary for the formation of the mature neuromuscular junction and has been shown to interact directly with rapsyn [16].
  • The AChR-associated protein rapsyn interacted with calpain in an agrin-dependent manner, and this interaction inhibited the protease activity of calpain [17].

Regulatory relationships of Rapsn


Other interactions of Rapsn

  • Thus, although both MuSK and rapsyn are required for AChR clustering in vivo, only rapsyn is essential for cluster formation per se [7].
  • Agrin-induced activation of acetylcholine receptor-bound Src family kinases requires Rapsyn and correlates with acetylcholine receptor clustering [19].
  • We report that newly synthesized rapsyn associates with the trans-Golgi network compartment and traffics via vesiculotubular organelles toward the cell surface of COS-7 cells [20].
  • Furthermore, when expressed in 293T cells, a rapsyn construct containing as few as two TPRs and the RING-H2 domain self-associates and clusters dystroglycan, but not nAChRs [16].
  • For mice lacking rapsyn, there is a failure of postsynaptic specialization characterized by an absence of nicotinic acetylcholine receptors (nAChRs) and other integral and peripheral membrane proteins such as beta-dystroglycan and utrophin [16].

Analytical, diagnostic and therapeutic context of Rapsn


  1. Chick ciliary ganglion neurons contain transcripts coding for acetylcholine receptor-associated protein at synapses (rapsyn). Burns, A.L., Benson, D., Howard, M.J., Margiotta, J.F. J. Neurosci. (1997) [Pubmed]
  2. Distinct roles of nerve and muscle in postsynaptic differentiation of the neuromuscular synapse. Lin, W., Burgess, R.W., Dominguez, B., Pfaff, S.L., Sanes, J.R., Lee, K.F. Nature (2001) [Pubmed]
  3. Failure of postsynaptic specialization to develop at neuromuscular junctions of rapsyn-deficient mice. Gautam, M., Noakes, P.G., Mudd, J., Nichol, M., Chu, G.C., Sanes, J.R., Merlie, J.P. Nature (1995) [Pubmed]
  4. Rapsyn is required for MuSK signaling and recruits synaptic components to a MuSK-containing scaffold. Apel, E.D., Glass, D.J., Moscoso, L.M., Yancopoulos, G.D., Sanes, J.R. Neuron (1997) [Pubmed]
  5. Expression of RAPsyn (43K protein) and nicotinic acetylcholine receptor genes is not coordinately regulated in mouse muscle. Frail, D.E., Musil, L.S., Buonanno, A., Merlie, J.P. Neuron (1989) [Pubmed]
  6. Characterization and mapping of the Rapsn gene encoding the 43-kDa acetylcholine receptor-associated protein. Gautam, M., Mudd, J., Copeland, N.G., Gilbert, D.J., Jenkins, N.A., Merlie, J.P. Genomics (1994) [Pubmed]
  7. Distinct phenotypes of mutant mice lacking agrin, MuSK, or rapsyn. Gautam, M., DeChiara, T.M., Glass, D.J., Yancopoulos, G.D., Sanes, J.R. Brain Res. Dev. Brain Res. (1999) [Pubmed]
  8. Identification of the mouse muscle 43,000-dalton acetylcholine receptor-associated protein (RAPsyn) by cDNA cloning. Frail, D.E., McLaughlin, L.L., Mudd, J., Merlie, J.P. J. Biol. Chem. (1988) [Pubmed]
  9. Increased ratio of rapsyn to ACh receptor stabilizes postsynaptic receptors at the mouse neuromuscular synapse. Gervásio, O.L., Phillips, W.D. J. Physiol. (Lond.) (2005) [Pubmed]
  10. Promotion of motoneuron survival and branching in rapsyn-deficient mice. Banks, G.B., Chau, T.N., Bartlett, S.E., Noakes, P.G. J. Comp. Neurol. (2001) [Pubmed]
  11. Regulation of the rapsyn promoter by kaiso and delta-catenin. Rodova, M., Kelly, K.F., VanSaun, M., Daniel, J.M., Werle, M.J. Mol. Cell. Biol. (2004) [Pubmed]
  12. Regulation of acetylcholine receptor clustering by the tumor suppressor APC. Wang, J., Jing, Z., Zhang, L., Zhou, G., Braun, J., Yao, Y., Wang, Z.Z. Nat. Neurosci. (2003) [Pubmed]
  13. The mammalian 43-kD acetylcholine receptor-associated protein (RAPsyn) is expressed in some nonmuscle cells. Musil, L.S., Frail, D.E., Merlie, J.P. J. Cell Biol. (1989) [Pubmed]
  14. Nitric oxide synthase (NOS-1) coclustered with agrin-induced AChR-specializations on cultured skeletal myotubes. Lück, G., Hoch, W., Hopf, C., Blottner, D. Mol. Cell. Neurosci. (2000) [Pubmed]
  15. Overexpression of rapsyn inhibits agrin-induced acetylcholine receptor clustering in muscle cells. Han, H., Noakes, P.G., Phillips, W.D. J. Neurocytol. (1999) [Pubmed]
  16. Interactions of the rapsyn RING-H2 domain with dystroglycan. Bartoli, M., Ramarao, M.K., Cohen, J.B. J. Biol. Chem. (2001) [Pubmed]
  17. Rapsyn interaction with calpain stabilizes AChR clusters at the neuromuscular junction. Chen, F., Qian, L., Yang, Z.H., Huang, Y., Ngo, S.T., Ruan, N.J., Wang, J., Schneider, C., Noakes, P.G., Ding, Y.Q., Mei, L., Luo, Z.G. Neuron (2007) [Pubmed]
  18. The synapse-associated protein rapsyn regulates tyrosine phosphorylation of proteins colocalized at nicotinic acetylcholine receptor clusters. Qu, Z., Apel, E.D., Doherty, C.A., Hoffman, P.W., Merlie, J.P., Huganir, R.L. Mol. Cell. Neurosci. (1996) [Pubmed]
  19. Agrin-induced activation of acetylcholine receptor-bound Src family kinases requires Rapsyn and correlates with acetylcholine receptor clustering. Mittaud, P., Marangi, P.A., Erb-Vögtli, S., Fuhrer, C. J. Biol. Chem. (2001) [Pubmed]
  20. Rapsyn escorts the nicotinic acetylcholine receptor along the exocytic pathway via association with lipid rafts. Marchand, S., Devillers-Thiéry, A., Pons, S., Changeux, J.P., Cartaud, J. J. Neurosci. (2002) [Pubmed]
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