Format

Send to

Choose Destination
Am J Physiol Cell Physiol. 2015 Jun 1;308(11):C919-31. doi: 10.1152/ajpcell.00029.2015. Epub 2015 Mar 25.

Creatine kinase B is necessary to limit myoblast fusion during myogenesis.

Author information

1
Graduate Program in Biochemistry, Cell and Developmental Biology, Emory University School of Medicine, Atlanta, Georgia; Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia; and.
2
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia; and.
3
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota.
4
Department of Pharmacology, Emory University School of Medicine, Atlanta, Georgia; and gpavlat@emory.edu.

Abstract

Myoblast fusion is critical for proper muscle growth and regeneration. During myoblast fusion, the localization of some molecules is spatially restricted; however, the exact reason for such localization is unknown. Creatine kinase B (CKB), which replenishes local ATP pools, localizes near the ends of cultured primary mouse myotubes. To gain insights into the function of CKB, we performed a yeast two-hybrid screen to identify CKB-interacting proteins. We identified molecules with a broad diversity of roles, including actin polymerization, intracellular protein trafficking, and alternative splicing, as well as sarcomeric components. In-depth studies of α-skeletal actin and α-cardiac actin, two predominant muscle actin isoforms, demonstrated their biochemical interaction and partial colocalization with CKB near the ends of myotubes in vitro. In contrast to other cell types, specific knockdown of CKB did not grossly affect actin polymerization in myotubes, suggesting other muscle-specific roles for CKB. Interestingly, knockdown of CKB resulted in significantly increased myoblast fusion and myotube size in vitro, whereas knockdown of creatine kinase M had no effect on these myogenic parameters. Our results suggest that localized CKB plays a key role in myotube formation by limiting myoblast fusion during myogenesis.

KEYWORDS:

actin; adenosine triphosphate; muscle growth; myocyte; myotube

PMID:
25810257
PMCID:
PMC4451350
DOI:
10.1152/ajpcell.00029.2015
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center