Richard L. Rotundo

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Aging is a major risk factor for metabolic disease and loss of skeletal muscle mass and strength, a condition known as sarcopenia. Both conditions present a major health burden to the elderly population. Here, we analyzed the effect of mildly increased PGC-1alpha expression in skeletal muscle during aging. We found that transgenic MCK-PGC-1alpha animals had(More)
The syntrophins are a family of structurally related proteins that contain multiple protein interaction motifs. Syntrophins associate directly with dystrophin, the product of the Duchenne muscular dystrophy locus, and its homologues. We have generated alpha-syntrophin null mice by targeted gene disruption to test the function of this association. The(More)
Formation of the synaptic basal lamina at vertebrate neuromuscular junction involves the accumulation of numerous specialized extracellular matrix molecules including a specific form of acetylcholinesterase (AChE), the collagenic-tailed form. The mechanisms responsible for its localization at sites of nerve- muscle contact are not well understood. To(More)
The dystrophin-associated protein (DAP) complex spans the sarcolemmal membrane linking the cytoskeleton to the basement membrane surrounding each myofiber. Defects in the DAP complex have been linked previously to a variety of muscular dystrophies. Other evidence points to a role for the DAP complex in formation of nerve-muscle synapses. We show that(More)
Acetylcholinesterase (AChE) is concentrated at the vertebrate neuromuscular synapse. To determine whether increased transcript levels could underlie this selective accumulation, we employed a quantitative reverse transcription polymerase chain reaction-based assay to determine mRNA copy number in samples as small as single neuromuscular junctions (NMJs) and(More)
Acetylcholinesterase (AChE) was the first identified synaptic component, characterized by its catalytic affinity for choline esters, and for a long time provided the conceptual scaffold for studies of the neuromuscular junction (NMJ). AChE was the first protein localized to the NMJ, in the 1930s, and its local expression shown to be regulated by the(More)
Tissue-cultured chicken embryo muscle cells synthesize several molecular forms of acetylcholinesterase (AChE) which differ in oligomeric structure and fate as membrane-bound or secreted molecules. Using irreversible inhibitors to inactivate AChE molecules we show that muscle cells rapidly synthesize and assemble catalytically active oligomers which transit(More)
The collagen-tailed form of acetylcholinesterase (AChE) is concentrated at the vertebrate neuromuscular junction (NMJ), where it is responsible for rapidly terminating neurotransmission. This unique oligomeric form of AChE, consisting of three tetramers covalently attached to a collagen-like tail, is more highly expressed in innervated regions of skeletal(More)
The major molecular form of acetylcholinesterase (AChE) from chicken brain is a membrane-bound glycoprotein with an apparent sedimentation coefficient of 11.4 S. Analysis of the purified protein by gel filtration, velocity sedimentation, and sodium dodecyl sulfate-gel electrophoresis shows that the solubilized enzyme is a globular tetramer with an apparent(More)
The syntrophins are a family of structurally related proteins that contain multiple protein interaction motifs. Syntrophins associate directly with dystrophin, the product of the Duchenne muscular dystrophy locus, and its homologues. We have generated a -syntrophin null mice by targeted gene disruption to test the function of this association. The a -Syn 2(More)