PUBLICATION
Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish
- Authors
- Housley, M.P., Njaine, B., Ricciardi, F., Stone, O.A., Hölper, S., Krüger, M., Kostin, S., Stainier, D.Y.
- ID
- ZDB-PUB-160614-5
- Date
- 2016
- Source
- PLoS Genetics 12: e1006099 (Journal)
- Registered Authors
- Housley, Michael, Stainier, Didier
- Keywords
- Skeletal muscles, Zebrafish, Larvae, Coated pits, Skeletal muscle fibers, Muscle proteins, Cell membranes, Swimming
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Caveolae/metabolism
- Caveolin 1/metabolism
- Caveolin 3/metabolism
- Extracellular Signal-Regulated MAP Kinases/metabolism
- Ion Channels/genetics
- Muscle Development/genetics*
- Muscle Proteins/genetics*
- Muscle Proteins/metabolism
- Muscle, Skeletal/embryology*
- Muscle, Skeletal/pathology*
- Muscular Dystrophies/genetics
- Zebrafish/embryology*
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 27294373 Full text @ PLoS Genet.
Citation
Housley, M.P., Njaine, B., Ricciardi, F., Stone, O.A., Hölper, S., Krüger, M., Kostin, S., Stainier, D.Y. (2016) Cavin4b/Murcb Is Required for Skeletal Muscle Development and Function in Zebrafish. PLoS Genetics. 12:e1006099.
Abstract
Skeletal muscles provide metazoans with the ability to feed, reproduce and avoid predators. In humans, a heterogeneous group of genetic diseases, termed muscular dystrophies (MD), lead to skeletal muscle dysfunction. Mutations in the gene encoding Caveolin-3, a principal component of the membrane micro-domains known as caveolae, cause defects in muscle maintenance and function; however it remains unclear how caveolae dysfunction underlies MD pathology. The Cavin family of caveolar proteins can form membrane remodeling oligomers and thus may also impact skeletal muscle function. Changes in the distribution and function of Cavin4/Murc, which is predominantly expressed in striated muscles, have been reported to alter caveolae structure through interaction with Caveolin-3. Here, we report the generation and phenotypic analysis of murcb mutant zebrafish, which display impaired swimming capacity, skeletal muscle fibrosis and T-tubule abnormalities during development. To understand the mechanistic importance of Murc loss of function, we assessed Caveolin-1 and 3 localization and found it to be abnormal. We further identified an in vivo function for Murc in Erk signaling. These data link Murc with developmental defects in T-tubule formation and progressive muscle dysfunction, thereby providing a new candidate for the etiology of muscular dystrophy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping