Journal article
ACTN3 genotype infuences muscle performance through the regulation of calcineurin signaling
JT Seto, KGR Quinlan, M Lek, XF Zheng, F Garton, DG Macarthur, MW Hogarth, PJ Houweling, P Gregorevic, N Turner, GJ Cooney, N Yang, KN North
Journal of Clinical Investigation | Published : 2013
DOI: 10.1172/JCI67691
Abstract
α-Actinin-3 deficiency occurs in approximately 16% of the global population due to homozygosity for a common nonsense polymorphism in the ACTN3 gene. Loss of α-actinin-3 is associated with reduced power and enhanced endurance capacity in elite athletes and nonathletes due to "slowing" of the metabolic and physiological properties of fast fibers. Here, we have shown that α-actinin-3 deficiency results in increased calcineurin activity in mouse and human skeletal muscle and enhanced adaptive response to endurance training. α-Actinin-2, which is differentially expressed in α-actinin-3-deficient muscle, has higher binding affinity for calsarcin-2, a key inhibitor of calcineurin activation. We ha..
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Awarded by National Health and Medical Research Council of Australia (NHMRC)
Awarded by Early Career Fellowships from the NHMRC of Australia
Awarded by Dora Lush Biomedical Scholarship from the NHMRC of Australia
Funding Acknowledgements
This project was funded in part by a grant from the National Health and Medical Research Council of Australia (NHMRC) (1002033). J.T. Seto and K.G.R. Quinlan are supported by Early Career Fellowships from the NHMRC of Australia (1036656 and 0511981). M. Lek and F. Garton are supported by Australian Postgraduate Awards. X.F. Zheng is supported by a Dora Lush Biomedical Scholarship from the NHMRC of Australia (1038991). N. Turner is supported by a Future Fellowship from the Australian Research Council. G.J. Cooney is supported by a Research Fellowship from the NHMRC of Australia. P. Gregorevic is supported by a Senior Research Fellowship sponsored by Pfizer Australia. The Baker IDI Heart and Diabetes Institute is supported in part by the Operational Infrastructure Support Program of the Victorian Government. We thank Hongwei Qian for the manufacture of the rAAV vectors.