PUBLICATION
Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity
- Authors
- Cao, J.M., Cheng, X.N., Li, S.Q., Heller, S., Xu, Z.G., Shi, D.L.
- ID
- ZDB-PUB-161110-16
- Date
- 2016
- Source
- Scientific Reports 6: 36768 (Journal)
- Registered Authors
- Shi, De-Li
- Keywords
- Extracellular matrix, Musculoskeletal development
- MeSH Terms
-
- Tumor Suppressor Proteins/metabolism
- Chickens
- Zebrafish
- Adaptor Proteins, Signal Transducing/metabolism
- Actins/metabolism
- Two-Hybrid System Techniques
- Gene Expression Profiling
- Animals
- Myoblasts/cytology*
- Vesicular Transport Proteins/metabolism
- Humans
- Protein Domains
- Oligonucleotides/genetics
- HEK293 Cells
- Golgi Apparatus/metabolism
- Myosins/chemistry
- Myosins/metabolism*
- Gene Expression Regulation
- Muscles/physiology*
- ras-GRF1/chemistry
- Cell Adhesion
- Protein Binding
- PubMed
- 27824130 Full text @ Sci. Rep.
Citation
Cao, J.M., Cheng, X.N., Li, S.Q., Heller, S., Xu, Z.G., Shi, D.L. (2016) Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity. Scientific Reports. 6:36768.
Abstract
The unconventional myosin MYO18A that contains a PDZ domain is required for muscle integrity during zebrafish development. However, the mechanism by which it functions in myofibers is not clear. The presence of a PDZ domain suggests that MYO18A may interact with other partners to perform muscle-specific functions. Here we performed double-hybrid screening and co-immunoprecipitation to identify MYO18A-interacting proteins, and have identified p190RhoGEF and Golgin45 as novel partners for the MYO18A PDZ domain. We have also identified Lurap1, which was previously shown to bind MYO18A. Functional analyses indicate that, similarly as myo18a, knockdown of lurap1, p190RhoGEF and Golgin45 by morpholino oligonucleotides disrupts dystrophin localization at the sarcolemma and produces muscle lesions. Simultaneous knockdown of myo18a with either of these genes severely disrupts myofiber integrity and dystrophin localization, suggesting that they may function similarly to maintain myofiber integrity. We further show that MYO18A and its interaction partners are required for adhesion of myoblasts to extracellular matrix, and for the formation of the Golgi apparatus and organization of F-actin bundles in myoblast cells. These findings suggest that MYO18A has the potential to form a multiprotein complex that links the Golgi apparatus to F-actin, which regulates muscle integrity and function during early development.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping