TY - JOUR
T1 - Control of myoblast fusion by a guanine nucleotide exchange factor, loner, and its effector ARF6
AU - Chen, Elizabeth
AU - Pryce, Brian A.
AU - Tzeng, Jarvis A.
AU - Gonzalez, Guillermo A.
AU - Olson, Eric N
N1 - Funding Information:
We thank Drs. Susan Abmayr, Dan Kiehart, Hanh Nguyen, Michael Roth, and the Developmental Studies Hybridoma Bank for cDNAs and antibodies; Minx Fuller, Devi Menon, Akinao Nose, Renate Renkawitz-Pohl and the Bloomington Stock Center for fly stocks. We thank Alisha Tizenor for graphics and Jennifer Page for editorial assistance. We appreciate Dennis McKearin, Duojia Pan, and Keith Wharton for insightful discussions and critical reading of the manuscript. E.H.C. was supported by a postdoctoral fellowship from the Helen Hay Whitney Foundation. This work was supported by grants from the National Institutes of Health and the D.W. Reynolds Center for Clinical Cardiovascular Research to E.N.O.
PY - 2003/9/19
Y1 - 2003/9/19
N2 - 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.
AB - 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.
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U2 - 10.1016/S0092-8674(03)00720-7
DO - 10.1016/S0092-8674(03)00720-7
M3 - Article
C2 - 14505574
AN - SCOPUS:0141426586
SN - 0092-8674
VL - 114
SP - 751
EP - 762
JO - Cell
JF - Cell
IS - 6
ER -