Acetylcholine Receptor: Complex of Homologous Subunits

Raftery, Michael A.; Hunkapiller, Michael W.; Strader, Catherine D.; Hood, Leroy

doi:10.1126/science.7384786

Cited by 588 publications

(285 citation statements)

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“…8 The nicotinic acetylcholine receptor (nAChR), a pentameric membrane protein complex of four homologous subunits with a molecular stoichiometry of a 2 , b, d, and g or e, is an important component of the NMJ. 9 Expression of the nAChR subunits and the distribution of these receptors among muscular fibers are regulated developmentally with nAChR gene expression at its highest levels during myogenic differentiation. 10 The muscle-specific receptor tyrosine kinase (MuSK) was discovered because of its abundance in the synapse-rich Torpedo electric organ and has been shown to be a key protein that orchestrates nAChR clustering and differentiation of the neuromuscular junction (NMJ).…”

Section: Introductionmentioning

confidence: 99%

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

Shen

Lee

et al. 2006

Journal Orthopaedic Research

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Botulinum toxin A (BoNT-A) is a potent biological toxin widely used for the management of skeletal muscle spasticity or dynamic joint contracture. Intramuscular injection of BoNT-A causes muscle denervation, paresis, and atrophy. This clinical effect of botulinum toxin A lasts 3 to 6 months, and injected muscle eventually regains muscle mass and recovers muscle function. The goal of the present study was to characterize the molecular and cellular mechanisms leading to neuromuscular junction (NMJ) regeneration and skeletal muscle functional recovery after BoNT-A injection. Fifty-six 1-month-old Sprague-Dawley rats were used. Botulinum toxin A was injected into the left gastrocnemius muscle at a dosage of 6 units/kg body weight. An equivalent volume of saline was injected into the right gastrocnemius muscle to serve as control. The gastrocnemius muscle samples were harvested from both hind limbs at 3 days, 7 days, 15 days, 30 days, 60 days, 90 days, 180 days, and 360 days after administration of toxin. In addition, the gastrocnemius muscles from 1-month-old rats with no injections were harvested to serve as uninjected control group. Muscle samples were processed and mRNA was extracted. Real-time polymerase chain reaction (PCR) and gene microarray technology were used to identify key molecules involved in NMJ stabilization and muscle functional recovery. More than 28,000 rat genes were analyzed and approximately 9000 genes are expressed in the rat gastrocnemius muscle. Seven days following BoNT-A injection, 105 genes were upregulated and 59 genes were downregulated. Key molecules involved in neuromuscular junction (NMJ) stabilization and muscle functional recovery were identified and their time course of gene expression following BoNT-A injection were characterized. This animal study demonstrates that following intramuscular injection of BoNT-A, there is a sequence of cellular events that eventually leads to NMJ stabilization, remodeling, and myogenesis and muscle functional recovery. This recovery process is divided into two stages (aneural and neural) and that the IGF-1 signaling pathway play a central role in the process. ß

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Section: Introductionmentioning

confidence: 99%

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

Shen

Lee

et al. 2006

Journal Orthopaedic Research

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“…The affinity of txin binding to the purified receptor was calculated from the rate constants determined from association and dissociation experiments and by Scdtchard analysis of saturation data. The affinities obtained are shown in ",able 6. In addition, the affinity'of toxin binding to receptor-rich To,,pedo OVS membranes determined from a saturation experiment with the solid phase assay P was 3.5 x.10-1 OM.…”

Section: Discussionmentioning

confidence: 99%

“…In the filter disk assay, 1 2 5 -BTX is incuuated with AChR in so 6 ut~igp. An aliquot of the solution is then placed on filter paper and unbound 1e I'-BTX, which does'not adhere to the filter paper, is washed away and bound radioactivity measured.…”

Section: %mentioning

confidence: 99%

Neurotoxin-Binding Site on The Acetylcholine Receptor

Lentz

Wilson

1988

International Review of Neurobiology

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“…22 Professor Numa at Kyoto University then used these sequences to clone the corresponding genes and started his now classical studies of receptors of the nervous system. So the highly sensitive protein sequencer opened up a multiplicity of new areas in biology through the sequence analyses of heretofore inaccessible proteins and the cloning of their corresponding genes.…”

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confidence: 99%

A Personal View of Molecular Technology and How It Has Changed Biology

Hood

2002

J. Proteome Res.

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I have had the pleasure of practicing biology and technology development for the past 35 yearssfirst at the National Institutes of Health (NIH) for 3 years, then at the California Institute of Technology (Caltech) for 22 years, subsequently at the University of Washington (UW) for 8 years, and finally at the Institute for Systems Biology (ISB) for the past 2 years. In each case, my geographical transitions were prompted by exciting new opportunities and evolving visions of how biology should be practiced. The technology developments I have been associated with over this period helped to catalyze two emerging paradigm changes in biology: systems biology and predictive/preventive medicine. Several points should be stressed regarding biology and technology. First, technology is all about deciphering biological information, and that information is of three general types: (1) the digital information of DNA; (2) the three-dimensional information of proteins, the molecular machines of life; and (3) the four-dimensional (time-variant) information of biological systems operating across developmental and/or physiological time spans. Second, biology should be the driver for new technologies. Where barriers to deciphering biological information exist, they need to be lifted by appropriate technologies. Third, technology includes new instrumentation (e.g., the automated DNA sequencer) as well as new strategies (e.g., the oligonucleotide ligase assay, or OLA). Finally, challenging new technologies often require the integration of expertise from biology, chemistry, computer science, engineering, mathematics, and physics. Especially important is the development and integration of computational tools for capturing, storing, and analyzing biological information.Throughout out my career, I have been associated with outstanding colleagues (Table 1), and it is to them that much of the credit must go for our accomplishments. It is with considerable pride that I note many of my former colleagues are today's technology leaders.Over my career, there have been six successive evolutionary stages to my thinking about biology and technology (Table 2). I will discuss each of these in turn.

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Acetylcholine Receptor: Complex of Homologous Subunits

Cited by 588 publications

References 59 publications

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

How muscles recover from paresis and atrophy after intramuscular injection of botulinum toxin A: Study in juvenile rats

Neurotoxin-Binding Site on The Acetylcholine Receptor

A Personal View of Molecular Technology and How It Has Changed Biology

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