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© The Rockefeller University Press, 0021-9525/1997//81 $5.00
The Journal of Cell Biology, Volume 138, Number 1, , 1997 81-93

Differential Association of Syntrophin Pairs with the Dystrophin Complex

Department of Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7545

The syntrophins are a multigene family of intracellular dystrophin-associated proteins comprising three isoforms, 1, β1, and β2. Based on their domain organization and association with neuronal nitric oxide synthase, syntrophins are thought to function as modular adapters that recruit signaling proteins to the membrane via association with the dystrophin complex. Using sequences derived from a new mouse β1-syntrophin cDNA, and previously isolated cDNAs for 1- and β2-syntrophins, we prepared isoform-specific antibodies to study the expression, skeletal muscle localization, and dystrophin family association of all three syntrophins. Most tissues express multiple syntrophin isoforms. In mouse gastrocnemius skeletal muscle, 1- and β1-syntrophin are concentrated at the neuromuscular junction but are also present on the extrasynaptic sarcolemma. β1-syntrophin is restricted to fast-twitch muscle fibers, the first fibers to degenerate in Duchenne muscular dystrophy. β2-syntrophin is largely restricted to the neuromuscular junction.

The sarcolemmal distribution of 1- and β1-syntrophins suggests association with dystrophin and dystrobrevin, whereas all three syntrophins could potentially associate with utrophin at the neuromuscular junction. Utrophin complexes immunoisolated from skeletal muscle are highly enriched in β1- and β2-syntrophins, while dystrophin complexes contain mostly 1- and β1-syntrophins. Dystrobrevin complexes contain dystrophin and 1- and β1-syntrophins. From these results, we propose a model in which a dystrophin–dystrobrevin complex is associated with two syntrophins. Since individual syntrophins do not have intrinsic binding specificity for dystrophin, dystrobrevin, or utrophin, the observed preferential pairing of syntrophins must depend on extrinsic regulatory mechanisms.

Address all correspondence to S.C. Froehner, Department of Physiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7545. Tel.: (919) 966-1239. Fax: (919) 966-6413. E-mail: froehner{at}med.unc.edu

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