Dataset Information
Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOS?.
Ontology highlight
ABSTRACT: Background
Loss of sarcolemmal nNOS? is a common manifestation in a wide variety of muscle diseases and contributes to the dysregulation of multiple muscle activities. Given the critical role sarcolemmal nNOS? plays in muscle, restoration of sarcolemmal nNOS? should be considered as an important therapeutic goal.Methods
nNOS? is anchored to the sarcolemma by dystrophin spectrin-like repeats 16 and 17 (R16/17) and the syntrophin PDZ domain (Syn PDZ). To develop a strategy that can independently restore sarcolemmal nNOS?, we engineered an R16/17-Syn PDZ fusion construct and tested whether this construct alone is sufficient to anchor nNOS? to the sarcolemma in three different mouse models of Duchenne muscular dystrophy (DMD).Results
Membrane-associated nNOS? is completely lost in DMD. Adeno-associated virus (AAV)-mediated delivery of the R16/17-Syn PDZ fusion construct successfully restored sarcolemmal nNOS? in all three models. Further, nNOS restoration was independent of the dystrophin-associated protein complex.Conclusions
Our results suggest that the R16/17-Syn PDZ fusion construct is sufficient to restore sarcolemmal nNOS? in the dystrophin-null muscle.
SUBMITTER: Patel A
PROVIDER: S-EPMC6251231 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Dystrophin R16/17-syntrophin PDZ fusion protein restores sarcolemmal nNOSμ.
Skeletal muscle 20181122 1
<h4>Background</h4>Loss of sarcolemmal nNOSμ is a common manifestation in a wide variety of muscle diseases and contributes to the dysregulation of multiple muscle activities. Given the critical role sarcolemmal nNOSμ plays in muscle, restoration of sarcolemmal nNOSμ should be considered as an important therapeutic goal.<h4>Methods</h4>nNOSμ is anchored to the sarcolemma by dystrophin spectrin-like repeats 16 and 17 (R16/17) and the syntrophin PDZ domain (Syn PDZ). To develop a strategy that can ...[more]