The distribution of nicotinic acetylcholine receptor (AChR) clusters at the cell membrane was studied in CHO-K1/A5 cells using fluorescence microscopy. Di-4-ANEPPDHQ, a fluorescent probe that differentiates between liquid-ordered (Lo) and liquid-disordered (Ld) phases in model membranes, was used in combination with monoclonal anti-AChR antibody labeling of live cells, which induces AChR cluste...

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 alpha7beta1 integrin is a major laminin receptor in skeletal muscle, we determined if this integrin participates in laminin and/or agrin-induced AChR clustering. The alter...

The nicotinic acetylcholine receptor (AChR) is phosphorylated on tyrosine both in vitro and in vivo. To identify the protein tyrosine kinase that phosphorylates the receptor, we have previously cloned and characterized two protein tyrosine kinases, Fyn and Fyk, that are highly expressed in Torpedo electric organ, a tissue enriched in the AChR. Both kinases were shown by coimmunoprecipitation to...

The two subtypes of mammalian muscle nicotinic acetylcholine receptors (AChR) are generated by the substitution of the 1 (adult) subunit for the g (fetal) subunit within the AChR pentamer. Null mutations of the adultAChR 1-subunit gene are themost commoncauseof theAChRdeficiencysyndrome. This is adisorder of neuromuscular transmission characterizedbynon-progressive fatigablemuscleweaknesspresen...

Experiments examining acetylcholine receptor (AChR) metabolism in tissue culture have hitherto been limited to animal systems. For many studies, the human AChR on human skeletal muscle provides a more physiologic target. However, previous studies suggested that the levels of AChR produced on cultured human muscle were inadequate for metabolic studies. We demonstrate here that the metabolism of ...

Neurology 2012;79:404–405 The skeletal muscle acetylcholine receptor (AChR) is a beautifully functional molecular complex made up of 5 subunits. Acetylcholine binding initiates pore opening, producing the endplate current (EPC); the resulting action potentials travel over the muscle surface and into the transverse tubules, initiating contraction via calcium (Ca ) release from the sarcoplasmic r...

Myasthenia gravis is an autoimmune disease characterized by circulating autoantibodies against the acetylcholine receptor (AChR) ~ present on the neuromuscular endplate. It is generally believed that these antibodies are responsible for an accelerated rate of AChR degradation, leading to muscular weakness and fatiguability (1). To date, treatment has involved either the administration of antich...

The patterning of skeletal muscle is thought to depend upon signals provided by motor neurons. We show that AChR gene expression and AChR clusters are concentrated in the central region of embryonic skeletal muscle in the absence of innervation. Neurally derived Agrin is dispensable for this early phase of AChR expression, but MuSK, a receptor tyrosine kinase activated by Agrin, is required to ...

We have examined the redistribution of acetylcholine receptor (AChR) intramembrane particles (IMPs) when AChR clusters of cultured rat myotubes are experimentally disrupted and allowed to reform. In control myotubes, the AChR IMPs are evenly distributed within the AChR domains of cluster membrane. Shortly after addition of azide to disrupt clusters, IMPs become unevenly scattered, with some mic...