Back to Search
Start Over
Sphingosine 1-Phosphate Induces Myoblast Differentiation through Cx43 Protein Expression: A Role for a Gap Junction-dependent and -independent Function
- Source :
- Molecular Biology of the Cell. 17:4896-4910
- Publication Year :
- 2006
- Publisher :
- American Society for Cell Biology (ASCB), 2006.
-
Abstract
- Although sphingosine 1-phosphate (S1P) has been considered a potent regulator of skeletal muscle biology, acting as a physiological anti-mitogenic and prodifferentiating agent, its downstream effectors are poorly known. In the present study, we provide experimental evidence for a novel mechanism by which S1P regulates skeletal muscle differentiation through the regulation of gap junctional protein connexin (Cx) 43. Indeed, the treatment with S1P greatly enhanced Cx43 expression and gap junctional intercellular communication during the early phases of myoblast differentiation, whereas the down-regulation of Cx43 by transfection with short interfering RNA blocked myogenesis elicited by S1P. Moreover, calcium and p38 MAPK-dependent pathways were required for S1P-induced increase in Cx43 expression. Interestingly, enforced expression of mutated Cx43Δ130–136reduced gap junction communication and totally inhibited S1P-induced expression of the myogenic markers, myogenin, myosin heavy chain, caveolin-3, and myotube formation. Notably, in S1P-stimulated myoblasts, endogenous or wild-type Cx43 protein, but not the mutated form, coimmunoprecipitated and colocalized with F-actin and cortactin in a p38 MAPK-dependent manner. These data, together with the known role of actin remodeling in cell differentiation, strongly support the important contribution of gap junctional communication, Cx43 expression and Cx43/cytoskeleton interaction in skeletal myogenesis elicited by S1P.
- Subjects :
- Myoblasts, Skeletal
Down-Regulation
Gene Expression
Connexin
Biology
p38 Mitogen-Activated Protein Kinases
Mice
Sphingosine
Myosin
medicine
Animals
Myocyte
Enzyme Inhibitors
Molecular Biology
Myogenin
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
Myogenesis
Electric Conductivity
Gap Junctions
Skeletal muscle
Actin remodeling
Cell Differentiation
Articles
Cell Biology
Cell biology
Cytoskeletal Proteins
Kinetics
Protein Transport
medicine.anatomical_structure
Connexin 43
biology.protein
lipids (amino acids, peptides, and proteins)
Calcium
Mutant Proteins
Lysophospholipids
Biomarkers
Cortactin
Protein Binding
Subjects
Details
- ISSN :
- 19394586 and 10591524
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Molecular Biology of the Cell
- Accession number :
- edsair.doi.dedup.....a4cd6e09576a47f3e2af547f25f493c1
- Full Text :
- https://doi.org/10.1091/mbc.e06-03-0243