| Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion. | |
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MedLine Citation:
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PMID: 18001711 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Atsushi Mukai; Naohiro Hashimoto |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-10-17 |
Journal Detail:
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Title: Experimental cell research Volume: 314 ISSN: 0014-4827 ISO Abbreviation: Exp. Cell Res. Publication Date: 2008 Jan |
Date Detail:
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Created Date: 2007-12-11 Completed Date: 2008-03-05 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 0373226 Medline TA: Exp Cell Res Country: United States |
Other Details:
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Languages: eng Pagination: 387-97 Citation Subset: IM |
Affiliation:
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Department of Regenerative Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Oobu, Aichi 474-8522, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Differentiation Cell Fusion Cells, Cultured Cyclic AMP / metabolism* Cyclic AMP-Dependent Protein Kinases / metabolism* Fluorescent Antibody Technique Forskolin / pharmacology Mice Muscle Cells / metabolism Muscle Fibers, Skeletal / cytology, enzymology* Stem Cells / cytology, metabolism |
| Chemical | |
Reg. No./Substance:
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60-92-4/Cyclic AMP; 66428-89-5/Forskolin; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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