Unknown

Dataset Information

0

Microtubule binding distinguishes dystrophin from utrophin.


ABSTRACT: Dystrophin and utrophin are highly similar proteins that both link cortical actin filaments with a complex of sarcolemmal glycoproteins, yet localize to different subcellular domains within normal muscle cells. In mdx mice and Duchenne muscular dystrophy patients, dystrophin is lacking and utrophin is consequently up-regulated and redistributed to locations normally occupied by dystrophin. Transgenic overexpression of utrophin has been shown to significantly improve aspects of the disease phenotype in the mdx mouse; therefore, utrophin up-regulation is under intense investigation as a potential therapy for Duchenne muscular dystrophy. Here we biochemically compared the previously documented microtubule binding activity of dystrophin with utrophin and analyzed several transgenic mouse models to identify phenotypes of the mdx mouse that remain despite transgenic utrophin overexpression. Our in vitro analyses revealed that dystrophin binds microtubules with high affinity and pauses microtubule polymerization, whereas utrophin has no activity in either assay. We also found that transgenic utrophin overexpression does not correct subsarcolemmal microtubule lattice disorganization, loss of torque production after in vivo eccentric contractions, or physical inactivity after mild exercise. Finally, our data suggest that exercise-induced inactivity correlates with loss of sarcolemmal neuronal NOS localization in mdx muscle, whereas loss of in vivo torque production after eccentric contraction-induced injury is associated with microtubule lattice disorganization.

SUBMITTER: Belanto JJ 

PROVIDER: S-EPMC3992671 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

altmetric image

Publications

Microtubule binding distinguishes dystrophin from utrophin.

Belanto Joseph J JJ   Mader Tara L TL   Eckhoff Michael D MD   Strandjord Dana M DM   Banks Glen B GB   Gardner Melissa K MK   Lowe Dawn A DA   Ervasti James M JM  

Proceedings of the National Academy of Sciences of the United States of America 20140331 15


Dystrophin and utrophin are highly similar proteins that both link cortical actin filaments with a complex of sarcolemmal glycoproteins, yet localize to different subcellular domains within normal muscle cells. In mdx mice and Duchenne muscular dystrophy patients, dystrophin is lacking and utrophin is consequently up-regulated and redistributed to locations normally occupied by dystrophin. Transgenic overexpression of utrophin has been shown to significantly improve aspects of the disease phenot  ...[more]

Similar Datasets

| S-EPMC3915414 | biostudies-literature
| S-EPMC5547154 | biostudies-literature
| S-EPMC2680620 | biostudies-literature
| S-EPMC3004926 | biostudies-literature
| S-EPMC3659351 | biostudies-literature
2007-12-13 | GSE6790 | GEO
| S-EPMC6586144 | biostudies-literature
| S-EPMC3439503 | biostudies-other
| S-EPMC3401230 | biostudies-literature
| S-EPMC9171417 | biostudies-literature