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| Status |
Public on Sep 06, 2017 |
| Title |
KLHL41 stabilizes skeletal muscle sarcomeres by nonproteolytic ubiquitination |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Maintenance of muscle function requires assembly of contractile proteins into highly organized sarcomeres. Mutations in Kelch-like protein 41 (KLHL41) cause nemaline myopathy, a fatal muscle disorder associated with sarcomere disarray. We generated KLHL41 mutant mice, which display lethal disruption of sarcomeres and aberrant expression of muscle structural and contractile proteins, mimicking the hallmarks of the human disease. We show that KLHL41 is poly-ubiquitinated and acts, at least in part, by preventing aggregation and degradation of nebulin, an essential component of the sarcomere. Furthermore, inhibition of KLHL41 poly-ubiquitination prevents its stabilization of nebulin, suggesting a unique role for ubiquitination in protein stabilization. These findings provide new insights into the molecular etiology of nemaline myopathy and reveal a mechanism whereby KLHL41 stabilizes sarcomeres and maintains muscle function by acting as a molecular chaperone. Similar mechanisms for protein stabilization likely contribute to the actions of other Kelch proteins.
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| Overall design |
Gene expression profile was generated comparing wild type (WT) and KLHL41 knockout mice, by deep sequencing, with three biological replicates, using Illumina HiSeq 2500.
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| Contributor(s) |
Ramirez-Martinez A, Olson EN |
| Citation(s) |
28826497 |
| |
| Submission date |
Mar 01, 2017 |
| Last update date |
May 15, 2019 |
| Contact name |
Andres Ramirez-Martinez |
| E-mail(s) |
andres.ramirezmartinez@utsouthwestern.edu
|
| Organization name |
UTSW Medical Center
|
| Department |
Molecular Biology
|
| Lab |
Olson Lab
|
| Street address |
6000 Harry Hines Blvd.
|
| City |
Dallas |
| State/province |
TX |
| ZIP/Postal code |
75390-9148 |
| Country |
USA |
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| Platforms (1) |
| GPL17021 |
Illumina HiSeq 2500 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA377410 |
| SRA |
SRP100902 |
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