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This Article Full Text Full Text (PDF) All Versions of this Article: 586/12/2841    most recent jphysiol.2008.151027v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by O'Connor, R. S. Articles by Pavlath, G. K. PubMed PubMed Citation Articles by O'Connor, R. S. Articles by Pavlath, G. K. Related Collections Cellular Related Article

¹ Department of Pharmacology, Emory University, Atlanta, GA 30322, USA
² Departments of Physiology and Radiology, Michigan State University, East Lansing, MI 48824, USA

Myoblast fusion is essential for muscle development, postnatal growth and muscle repair after injury. Recent studies have demonstrated roles for actin polymerization during myoblast fusion. Dynamic cytoskeletal assemblies directing cell–cell contact, membrane coalescence and ultimately fusion require substantial cellular energy demands. Various energy generating systems exist in cells but the partitioning of energy sources during myoblast fusion is unknown. Here, we demonstrate a novel role for phosphocreatine (PCr) as a spatiotemporal energy buffer during primary mouse myoblast fusion with nascent myotubes. Creatine treatment enhanced cell fusion in a creatine kinase (CK)-dependent manner suggesting that ATP-consuming reactions are replenished through the PCr/CK system. Furthermore, selective inhibition of actin polymerization prevented myonuclear addition following creatine treatment. As myotube formation is dependent on cytoskeletal reorganization, our findings suggest that PCr hydrolysis is coupled to actin dynamics during myoblast fusion. We conclude that myoblast fusion is a high-energy process, and can be enhanced by PCr buffering of energy demands during actin cytoskeletal rearrangements in myoblast fusion. These findings implicate roles for PCr as a high-energy phosphate buffer in the fusion of multiple cell types including sperm/oocyte, trophoblasts and macrophages. Furthermore, our results suggest the observed beneficial effects of oral creatine supplementation in humans may result in part from enhanced myoblast fusion.

(Received 10 January 2008; accepted after revision 14 April 2008; first published online 17 April 2008)
Corresponding author G. Pavlath: Emory University, Department of Pharmacology, 1510 Clifton Rd, Room 5027, Atlanta, GA 30322, USA. Email: gpavlat{at}emory.edu

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