ZFIN ID: ZDB-PUB-161110-16
Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity
Cao, J.M., Cheng, X.N., Li, S.Q., Heller, S., Xu, Z.G., Shi, D.L.
Date: 2016
Source: Scientific Reports   6: 36768 (Journal)
Registered Authors: Shi, De-Li
Keywords: Extracellular matrix, Musculoskeletal development
MeSH Terms:
  • Actins/metabolism
  • Adaptor Proteins, Signal Transducing/metabolism
  • Animals
  • Cell Adhesion
  • Chickens
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Golgi Apparatus/metabolism
  • HEK293 Cells
  • Humans
  • Muscles/physiology*
  • Myoblasts/cytology*
  • Myosins/chemistry
  • Myosins/metabolism*
  • Oligonucleotides/genetics
  • Protein Binding
  • Protein Domains
  • Tumor Suppressor Proteins/metabolism
  • Two-Hybrid System Techniques
  • Vesicular Transport Proteins/metabolism
  • Zebrafish
  • ras-GRF1/chemistry
PubMed: 27824130 Full text @ Sci. Rep.
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.