RASSF4 is required for skeletal muscle differentiation

RASSF4, a member of the classical RASSF family of scaffold proteins, is associated with alveolar rhabdomyosarcoma, an aggressive pediatric cancer of muscle histogenesis. However, the role of RASSF4 in normal myogenesis is unknown. We demonstrate here that RASSF4 is necessary for early in vitro myoge...

Full description

Saved in:
Bibliographic Details
Published in:Cell biology international 2020-02, Vol.44 (2), p.381-390
Main Authors: Lin, Yi‐Tzu, Deel, Michael D., Linardic, Corinne M.
Format: Article
Language:English
Subjects:
Alveoli
Cell Differentiation
Cells, Cultured
Histogenesis
Humans
microtubule
Muscle Development
Muscle, Skeletal - cytology
Muscle, Skeletal - metabolism
Myoblasts
Myoblasts - cytology
Myoblasts - metabolism
Myogenesis
myogenic differentiation
Myogenin
Myotubes
Pediatrics
RASSF4
Rhabdomyosarcoma
Signal Transduction
Skeletal muscle
Tumor Suppressor Proteins - metabolism
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:RASSF4, a member of the classical RASSF family of scaffold proteins, is associated with alveolar rhabdomyosarcoma, an aggressive pediatric cancer of muscle histogenesis. However, the role of RASSF4 in normal myogenesis is unknown. We demonstrate here that RASSF4 is necessary for early in vitro myogenesis. Using primary human myoblasts, we show that RASSF4 expression is dramatically increased during in vitro myogenic differentiation, and conversely that RASSF4‐deficient myoblasts cannot differentiate, potentially because of a lack of upregulation of myogenin. In microscopy studies, we show that RASSF4 protein co‐localizes with proteins of the myogenic microtubule‐organizing center (MTOC) both before and after myogenic differentiation. RASSF4‐deficient cells subject to differentiation conditions demonstrate a lack of shape change, suggesting that RASSF4 plays a role in promoting microtubule reorganization and myoblast elongation. In biochemical studies of myotubes, RASSF4 associates with MST1, suggesting that RASSF4 signals to MST1 in the myogenic differentiation process. Expression of MST1 in myoblasts partially reversed the effect of RASSF4 knockdown on differentiation, suggesting that RASSF4 and MST1 coordinately support myogenic differentiation. These data show that RASSF4 is critical for the early steps of myogenic differentiation.
ISSN:1065-6995
1095-8355
DOI:10.1002/cbin.11238