At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMN...

The distribution of acetylcholine receptors (AChRs) within and around the neuromuscular junction changes dramatically during the first postnatal weeks, a period during which polyneuronal innervation is eliminated. We reported previously that protein kinase C (PKC) activation accelerates postnatal synapse loss. Because of the close relationship between axonal retraction and AChR cluster dispersa...

Purpose To investigate the relation between type of motor endplate, acetylcholine receptor (AChR) subunit composition, and fiber types in human extraocular muscles (EOMs). Methods EOM samples collected from subjects aged 34 to 82 years were serially sectioned and processed for immunohistochemistry, with specific antibodies against different myosin heavy chain (MyHC) isoforms, neurofilament, s...

We have examined the properties and intracellular localization of acetylcholine receptors in the C2 muscle cell line and in a variant (T-) that accumulates AChR intracellularly. On immunoblots, the subunit structures of the AChR from wild-type and Tcells were similar except that the 3' and t5 subunits of the variant AChR had altered mobilities. Digestion with endoglycosidases H and F demonstrat...

We have noted previously that duration of vecuronium block correlated with fibre size in six muscle groups in the goat. Electrophysiological considerations suggest that the important factor should be the number of acetylcholine receptors (AChR) relative to fibre size. However, this hypothesis could not be verified in the goat because the number of AChR was relatively constant in the different m...

Myasthenia gravis (MG) is mediated by autoantibodies to the acetylcholine receptor (AChR), expressed in muscle and rare thymic myoid cells. Most early-onset cases show thymic lymph node-type infiltrates, including pre-activated plasma cells spontaneously producing anti-AChR antibodies. Since these are not evident in the associated thymomas found in another 10% of MG patients, AChR-specific B ce...

Objective To evaluate the relationship between clinical improvement in Myasthenia Gravis-Activities of Daily Living (MG-ADL) scores and pharmacodynamic effects IgG autoantibody lowering induced by nipocalimab Vivacity MG Phase 2 study. Background Nipocalimab is a fully human, aglycosylated, effectorless IgG1 anti-FcRn monoclonal antibody that targets neonatal Fc receptor (FcRn) with high affini...

Background: Efgartigimod, a human IgG1 antibody Fc-fragment, reduces IgG levels through neonatal Fc receptor blockade. Patients with anti-acetylcholine antibody–negative (AChR-Ab–) generalized myasthenia gravis (gMG) comprise 15%-20% of the gMG population and have limited approved treatment options. We evaluated long-term safety efficacy efgartigimod in AChR-Ab– patients from ADAPT/ADAPT+ (open...

Agrin activates the transmembrane tyrosine kinase MuSK to mediate acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ). However, the intracellular signaling mechanism downstream of MuSK is poorly characterized. This study provides evidence that geranylgeranyltransferase I (GGT) is an important signaling component in the Agrin/MuSK pathway. Agrin causes a rapid increase i...

The fourth transmembrane domain (M4) of the nicotinic acetylcholine receptor (AChR) contributes to the kinetics of activation, yet its close association with the lipid bilayer makes it the outermost of the transmembrane domains. To investigate mechanistic and structural contributions of M4 to AChR activation, we systematically mutated alphaT422, a conserved residue that has been labeled by hydr...