Identification of novel MYO18A interaction partners required for myoblast adhesion and muscle integrity

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-spec...

Full description

Saved in:
Bibliographic Details
Published in:Scientific reports 2016-11, Vol.6 (1), p.36768-36768, Article 36768
Main Authors: Cao, Jian-Meng, Cheng, Xiao-Ning, Li, Shang-Qi, Heller, Stefan, Xu, Zhi-Gang, Shi, De-Li
Format: Article
Language:English
Subjects:
14/19
631/136/2060/2068
631/80/79/750
64/116
Actin
Adhesion
Development Biology
Dystrophin
Extracellular matrix
Golgi apparatus
Humanities and Social Sciences
Immunoprecipitation
Life Sciences
Localization
multidisciplinary
Myoblasts
Myosin
Oligonucleotides
Sarcolemma
Science
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/srep36768