The 43 kDa AChR-associated protein rapsyn is required for the clustering of nicotinic acetylcholine receptors (AChRs) at the developing neuromuscular junction, but the functions of other postsynaptic proteins colocalized with the AChR are less clear. Here we use a fibroblast expression system to investigate the role of the dystrophin-glycoprotein complex (DGC) in AChR clustering. The agrin-bind...

At the developing neuromuscular junction, a motoneuron-derived factor called agrin signals through the muscle-specific kinase receptor to induce postsynaptic aggregation of the acetylcholine receptor (AChR). The agrin signaling pathway involves tyrosine phosphorylation of the AChR beta subunit, and we have tested its role in receptor localization by expressing tagged, tyrosine-minus forms of th...

The clustering of acetylcholine receptors (AChR) in the postsynaptic membrane is an early event in the formation of the neuromuscular junction. The mechanism of clustering is still unknown, but is generally believed to be mediated by the postsynaptic cytoskeleton. We have identified an unusual isoform of beta-spectrin which colocalizes with AChR in AChR clusters isolated from rat myotubes in vi...

OBJECTIVES To report the characteristics of juvenile-onset (<20 years) myasthenia gravis (MG) in Africa. SUBJECTS AND METHODS Six South African centres collected data which included acetylcholine receptor-antibody (AChR-ab) status, delay before diagnosis, MG Foundation of America grade at onset, maximum severity and severity at last visit, therapies, outcomes and complications. RESULTS We r...

We report the lateral mobility of extrajunctional acetylcholine receptors (AChR), marked with fluorescently labeled alpha-bungarotoxin, on rat flexor digitorum brevis single muscle fibers maintained in cell culture. Mobility is measured by a modification of the fluorescence photobleaching recovery technique. The denervated rat flexor digitorum brevis muscle fibers exhibit a nonuniform distribut...

Stability of the nicotinic acetylcholine receptor (AChR) at the cell surface is key to the correct functioning of the cholinergic synapse. Cholesterol (Chol) is necessary for homeostasis of AChR levels at the plasmalemma and for ion translocation. Here we characterize the endocytic pathway followed by muscle-type AChR in Chol-depleted cells (Chol(-)). Under such conditions, the AChR is internal...

The clustering of nicotinic acetylcholine receptors (AChRs) is one of the first events observed during formation of the neuromuscular junction. To determine the mechanism involved in AChR clustering, we established a nonmuscle cell line (mouse fibroblast L cells) that stably expresses just one muscle-specific gene product, the AChR. We have shown that when Torpedo californica AChRs are expresse...

We have investigated the mechanisms regulating the clustering of nicotinic acetylcholine receptor (AChR) on the surface of cultured embryonic chick muscle cells. Treatment of these cells with the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), a potent activator of protein kinase C, was found to cause a rapid dispersal of AChR clusters, as monitored by fluorescence microscopy of cells...

In adult skeletal muscle, the nicotinic acetylcholine receptor (AChR) specifically accumulates at the neuromuscular junction, to allow neurotransmission. This clustering is paralleled by a compartmentalization of AChR genes expression to subsynaptic nuclei, which acquire a unique gene expression program and a specific morphology in response to neural cues. Our results demonstrate that neural ag...

The clustering of acetylcholine receptors (AChR) on skeletal muscle fibers is an early event in the formation of neuromuscular junctions. Recent studies show that laminin as well as agrin can induce AChR clustering. Since the a 7 b 1 integrin is a major laminin receptor in skeletal muscle, we determined if this integrin participates in laminin and/or agrin-induced AChR clustering. The alternati...