Syntrophin isoforms at the neuromuscular junction: developmental time course and differential localization.
The syntrophins are a family of cytoplasmic adapter proteins that associate with dystrophin family proteins and have putative signaling and structural roles at the neuromuscular junction. We have localized the syntrophin family members within the rodent junction from birth to adulthood. Alpha-syntrophin is the only isoform on the postsynaptic membrane at birth. In the adult, it occurs on the crests of the junctional folds, with utrophin, and in the troughs, with dystrophin. Surprisingly, neuronal nitric oxide synthase (nNOS) does not accompany alpha-syntrophin onto the crests. Beta2-syntrophin, a junction-specific form, is not present at birth and occurs mainly in the troughs in the adult. Beta1-syntrophin is a sarcolemmal form at birth, not concentrated at the junction, and disappears entirely from most fibers by 6 weeks. In positive fibers, junctional beta1-syntrophin occurs exclusively in the troughs. These results suggest that the syntrophin isoforms have distinct functions at the junction and show that the known protein-protein associations of the syntrophins and nNOS in skeletal muscle are not sufficient to explain their localizations.
Kramarcy
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Department of Cell and Molecular Physiology, University of North Carolina, Chapel Hill, North Carolina 27599, USA.
Sealock
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R
D000818:Animals; D003598:Cytoskeletal Proteins / Q000032:analysis; D003714:Denervation; D049029:Dystrophin-Associated Proteins; D018507:Gene Expression Regulation, Developmental; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009124:Muscle Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D009469:Neuromuscular Junction / Q000737:chemistry / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011817:Rabbits; D051381:Rats; D012508:Sarcolemma / Q000737:chemistry; D049411:Utrophin
D003598:Cytoskeletal Proteins; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; C483600:Utrn protein, mouse; D049411:Utrophin; C091824:syntrophin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; C496322:Nos1 protein, rat