Receptor-Associated Protein of The Synapse Proteine (RAPSN)

Human Receptor-Associated Protein of The Synapse (RAPSN) Interaktionspartner

1. Report attributes the RAPSN mutation c.484G > A, identified in a homozygous state, to causing fetal akinesia deformation sequence.

2. Mutations in RAPSN and COLQ are the most common causes of congenital myasthenic syndrome in Israel.

3. Hypomethylation of CpG sites in RPTOR, MGRN1 and RAPSN in blood is associated with breast cancer.

4. These findings uncover a new link between rapsyn, lysosome positioning, exocytosis and plasma membrane integrity.

5. Two siblings affected with typical congenital myasthenic syndrome harbor the common heterozygous (-38A-G) E-box mutation associated with a previously unreported heterozygous p.224 insT, causing an insertion of threonine in the TPR6 domain.

6. a mutation of the RAPSN gene may have a role in development of congenital myasthenic syndrome after general anaesthesia [case report]

7. Investigation of mutations in RAPSN determines that patients with congenital myasthenic syndrome can be misdiagnosed with seronegative myasthenia gravis.

8. An allelic quantification on patient's DNA identified three novel multi-exon deletions of RAPSN.

9. nAChR mobility in plasma membranes of myoblast cells during their differentiation to myotubes in the presence and absence of rapsyn

10. Rapsyn mutations in humans cause endplate acetylcholine-receptor deficiency and myasthenic syndrome

11. E-box mutations in the RAPSN promoter region may have a role in congenital myasthenic syndrome

12. Four patients from four different families with RAPSN mutations and congenital myasthenic syndrome

13. Twenty patients with the recessive form of congenital myasthenic syndrome with no mutations in the AChR subunit have been tested for this gene; five patients have been found to carry mutations.

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

15. recombination events may have occurred within the rapsyn gene and that this may have implications in the phenotypic expression of postsynaptic congenital myasthenic syndrome

16. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin.

17. The patient presents with an early onset sporadic congenital myasthenic syndrome was found The mutation RAPSN N88K was found heterozygously to a large deletion of about 4.5 kb disrupting the RAPSN gene.

18. Screening for the common mutation RAPSN N88K facilitates targeted genetic analysis in congenital myasthenic syndromes.

19. No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence.

20. All but 1 patient presented early in life and most responded to cholinergic agonists. With early diagnosis and therapy, rapsyn deficiency has a benign course in most patients.

Mouse (Murine) Receptor-Associated Protein of The Synapse (RAPSN) Interaktionspartner

1. The RING domain of rapsyn contains E3 ligase activity. Mutation of the RING domain that abolishes the enzyme activity inhibits rapsyn- as well as agrin-induced AChR clustering in heterologous and muscle cells. Further biological and genetic studies support a working model where rapsyn, a classic scaffold protein, serves as an E3 ligase to induce AChR clustering and NMJ formation, possibly by regulation of AChR neddylation

2. Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3gamma, and Dok-7 proteins and phosphorylates the latter two.

3. Plectin bridges acetylcholine receptors and intermediate filaments via direct interaction with the AChR-scaffolding protein rapsyn in an isoform-specific manner.

4. Molecular modelling, immunoprecipitation and bimolecular fluorescence complementation approaches identify an alpha-helical stretch of rapsyn to be crucial for binding to the dimerisation and docking domain of PKA type I.

5. typical anchoring proteins of central excitatory synapses coimmunoprecipitate and colocalize with rapsyn

6. alpha-Actinin, rapsyn, and surface AChR form a ternary complex.

7. nAChR mobility in plasma membranes of myoblast cells during their differentiation to myotubes in the presence and absence of rapsyn

8. These results provide the first experimental evidence that rapsyn is a direct sequence-specific target of Kaiso and delta-catenin.

9. Thus, the metabolic half-life of receptors at the synapse may be modulated by local changes in the subsynaptic ratio of rapsyn to AChR.

10. Remarkable dynamism of rapsyn underlies stability and maintenance of the postsynaptic scaffold and suggests that the insertion of different postsynaptic proteins may be operating independently.

11. Developmental increase in the amount of rapsyn per acetylcholine receptor promotes postsynaptic receptor packing and stability.

12. Beta-catenin interacts with rapsyn, a molecule key for acetylcholine receptor clustering in motoneurons at the neuromuscular junction.

13. Rapsyn stabilizes acetylcholine receptor clusters at the neuromuscular junction by suppressing calpain activity.

14. At the postnatal neuromuscular synapse agrin signaling elevates the expression and targeting of rapsyn to the postsynaptic membrane, thereby packing more AChRs into stable, functionally-important AChR aggregates.

15. Wnt/beta-catenin signaling plays a negative role for postsynaptic differentiation at the neuromuscular junction, probably by regulating the expression of synaptic proteins, such as Rapsyn

16. Rapsyn interacts with the acetylcholine receptor via an alpha-helical structural motif. Binding at this site likely mediates the critical rapsyn interaction involved in localizing the acetylcholine receptor at the neuromuscular junction.

Zebrafish Receptor-Associated Protein of The Synapse (RAPSN) Interaktionspartner

1. Our findings indicate that the reduced postsynaptic receptor density resulting from defective rapsyn contributes to weakness, but is not solely responsible for use-dependent fatigue