Document Detail

Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion.
MedLine Citation:
PMID:  18001711     Owner:  NLM     Status:  MEDLINE    
Multinucleated myotubes are formed by fusion of mononucleated myogenic progenitor cells (myoblasts) during terminal skeletal muscle differentiation. In addition, myoblasts fuse with myotubes, but terminally differentiated myotubes have not been shown to fuse with each other. We show here that an adenylate cyclase activator, forskolin, and other reagents that elevate intracellular cyclic AMP (cAMP) levels induced cell fusion between small bipolar myotubes in vitro. Then an extra-large myotube, designated a "myosheet," was produced by both primary and established mouse myogenic cells. Myotube-to-myotube fusion always occurred between the leading edge of lamellipodia at the polar end of one myotube and the lateral plasma membrane of the other. Forskolin enhanced the formation of lamellipodia where cAMP-dependent protein kinase (PKA) was accumulated. Blocking enzymatic activity or anchoring of PKA suppressed forskolin-enhanced lamellipodium formation and prevented fusion of multinucleated myotubes. Localized PKA activity was also required for fusion of mononucleated myoblasts. The present results suggest that localized PKA plays a pivotal role in the early steps of myogenic cell fusion, such as cell-to-cell contact/recognition through lamellipodium formation. Furthermore, the localized cAMP-PKA pathway might be involved in the specification of the fusion-competent areas of the plasma membrane in lamellipodia of myogenic cells.
Atsushi Mukai; Naohiro Hashimoto
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-10-17
Journal Detail:
Title:  Experimental cell research     Volume:  314     ISSN:  0014-4827     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2007-12-11     Completed Date:  2008-03-05     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  387-97     Citation Subset:  IM    
Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522, Japan.
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MeSH Terms
Cell Differentiation
Cell Fusion
Cells, Cultured
Cyclic AMP / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism*
Fluorescent Antibody Technique
Forskolin / pharmacology
Muscle Cells / metabolism
Muscle Fibers, Skeletal / cytology,  enzymology*
Stem Cells / cytology,  metabolism
Reg. No./Substance:
60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC AMP-Dependent Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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