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Author Notes:

Corresponding author G. Pavlath: Emory University, Department of Pharmacology, 1510 Clifton Rd, Room 5027, Atlanta, GA 30322, USA. Email: gpavlat@emory.edu

Author's present address R. S. O'Connor: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

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Research Funding:

This work was supported by grants AR052730, AR047314, AR051372 from the National Institutes of Health and the Muscular Dystrophy Association to G.K.P., and MA 00210 from the National Space Biomedical Research Institute to RWW.

Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion

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Journal Title:

Journal of Physiology

Volume:

Volume 586, Number Pt 12

Publisher:

, Pages 2841-2853

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2008 The Authors. Journal compilation © 2008 The Physiological Society

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