Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6

Elizabeth Chen, Brian A. Pryce, Jarvis A. Tzeng, Guillermo A. Gonzalez, Eric N Olson

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

Myoblast fusion is essential for the formation and regeneration of skeletal muscle. In a genetic screen for regulators of muscle development in Drosophila, we discovered a gene encoding a guanine nucleotide exchange factor, called loner, which is required for myoblast fusion. Loner localizes to subcellular sites of fusion and acts downstream of cell surface fusion receptors by recruiting the small GTPase ARF6 and stimulating guanine nucleotide exchange. Accordingly, a dominant-negative ARF6 disrupts myoblast fusion in Drosophila embryos and in mammalian myoblasts in culture, mimicking the fusion defects caused by loss of Loner. Loner and ARF6, which also control the proper membrane localization of another small GTPase, Rac, are key components of a cellular apparatus required for myoblast fusion and muscle development. In muscle cells, this fusigenic mechanism is coupled to fusion receptors; in other fusion-competent cell types it may be triggered by different upstream signals.

Original languageEnglish (US)
Pages (from-to)751-762
Number of pages12
JournalCell
Volume114
Issue number6
DOIs
StatePublished - Sep 19 2003

Fingerprint

Guanine Nucleotide Exchange Factors
Myoblasts
Fusion reactions
Monomeric GTP-Binding Proteins
Muscle Development
Cell Fusion
Muscle
Drosophila
Mammalian Embryo
Guanine Nucleotides
Cell Surface Receptors
Muscle Cells
Regeneration
Skeletal Muscle
Gene encoding
Membranes
Genes
Cells
Defects

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. / Chen, Elizabeth; Pryce, Brian A.; Tzeng, Jarvis A.; Gonzalez, Guillermo A.; Olson, Eric N.

In: Cell, Vol. 114, No. 6, 19.09.2003, p. 751-762.

Research output: Contribution to journalArticle

Chen, Elizabeth ; Pryce, Brian A. ; Tzeng, Jarvis A. ; Gonzalez, Guillermo A. ; Olson, Eric N. / Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6. In: Cell. 2003 ; Vol. 114, No. 6. pp. 751-762.
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