A Highlights from MBoC Selection: Nucleotide- and Protein-Dependent Functions of Actg1 |
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Authors: | Lauren J. Sundby,William M. Southern,Katelin M. Hawbaker,Jesú s M. Trujillo,Benjamin J. Perrin,James M. Ervasti |
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Affiliation: | Yale University;aProgram in Molecular, Cellular, Developmental Biology, and Genetics, and;bDepartment of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, MN 55455;cDepartment of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46022 |
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Abstract: | Cytoplasmic β- and γ-actin proteins are 99% identical but support unique organismal functions. The cytoplasmic actin nucleotide sequences Actb and Actg1, respectively, are more divergent but still 89% similar. Actb–/– mice are embryonic lethal and Actb–/– cells fail to proliferate, but editing the Actb gene to express γ-actin (Actbc–g) resulted in none of the overt phenotypes of the knockout revealing protein-independent functions for Actb. To determine if Actg1 has a protein-independent function, we crossed Actbc–g and Actg1–/– mice to generate the bG/0 line, where the only cytoplasmic actin expressed is γ-actin from Actbc–g. The bG/0 mice were viable but showed a survival defect despite expressing γ-actin protein at levels no different from bG/gG with normal survival. A unique myopathy phenotype was also observed in bG/0 mice. We conclude that impaired survival and myopathy in bG/0 mice are due to loss of Actg1 nucleotide-dependent function(s). On the other hand, the bG/0 genotype rescued functions impaired by Actg1–/–, including cell proliferation and auditory function, suggesting a role for γ-actin protein in both fibroblasts and hearing. Together, these results identify nucleotide-dependent functions for Actg1 while implicating γ-actin protein in more cell-/tissue-specific functions. |
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