ACTN3 genotype infuences muscle performance through the regulation of calcineurin signaling

Journal of Clinical Investigation

Volumn 123, Issue 10, 2013, Pages 4255-4263

  Seto, Jane T ^a,b   Quinlan, Kate G R ^a,b   Lek, Monkol ^a,b   Zheng, Xi Fiona ^a,b   Garton, Fleur ^a,b   Macarthur, Daniel G ^a,b   Hogarth, Marshall W ^a,b   Houweling, Peter J ^a,b   Gregorevic, Paul ^c   Turner, Nigel ^d,e   Cooney, Gregory J ^d,e   Yang, Nan ^a,b   North, Kathryn N ^a,b,f  

^a CHILDREN S HOSPITAL AT WESTMEAD   (Australia)

^b University of Sydney   (Australia)

^c BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^d GARVAN INSTITUTE OF MEDICAL RESEARCH   (Australia)

^e UNIVERSITY OF NEW SOUTH WALES   (Australia)

^f ROYAL CHILDREN'S HOSPITAL   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA ACTININ 3; CALCINEURIN; CALSARCIN 2; PROTEIN; UNCLASSIFIED DRUG; ACTIN BINDING PROTEIN; ACTININ; ACTN3 PROTEIN, HUMAN; CARRIER PROTEIN; MUSCLE PROTEIN; MYOZ1 PROTEIN, MOUSE; PROTEIN BINDING;

ADAPTATION; ADULT; AGED; ANIMAL EXPERIMENT; ARTICLE; BINDING AFFINITY; BINDING SITE; CLINICAL ARTICLE; CONTROLLED STUDY; ENDURANCE TRAINING; ENZYME ACTIVITY; FAST MUSCLE FIBER; FEMALE; GENOTYPE; GRIP STRENGTH; HUMAN; MOLECULAR MECHANICS; MOUSE; MUSCLE FUNCTION; NEGATIVE FEEDBACK; NONHUMAN; PHENOTYPE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; SKELETAL MUSCLE; UPREGULATION; 129 MOUSE; ANIMAL; BINDING COMPETITION; C57BL MOUSE; CALCIUM SIGNALING; CHLOROCEBUS AETHIOPS; COS 1 CELL LINE; ENDURANCE; GENETIC ASSOCIATION; GENETICS; KNOCKOUT MOUSE; MALE; METABOLISM; MIDDLE AGED; MUSCLE STRENGTH; PHYSIOLOGY;

ACTININ; ADAPTATION, PHYSIOLOGICAL; ADULT; AGED; ANIMALS; BINDING, COMPETITIVE; CALCINEURIN; CALCIUM SIGNALING; CARRIER PROTEINS; CERCOPITHECUS AETHIOPS; COS CELLS; FEMALE; GENETIC ASSOCIATION STUDIES; GENOTYPE; HUMANS; MALE; MICE; MICE, 129 STRAIN; MICE, INBRED C57BL; MICE, KNOCKOUT; MICROFILAMENT PROTEINS; MIDDLE AGED; MUSCLE PROTEINS; MUSCLE STRENGTH; MUSCLE, SKELETAL; PHYSICAL CONDITIONING, ANIMAL; PHYSICAL ENDURANCE; PROTEIN BINDING;

EID: 84885063954     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI67691     Document Type: Article

References (39)

1. MacArthur DG, North KN. A gene for speed? The evolution and function of α-actinin-3. Bioessays. 2004;26(7):786-795.
2. Houweling PJ, North KN. Sarcomeric α-actinins and their role in human muscle disease. Future Neurol. 2009;4(6):731-743.
3. Lek M, North KN. Are biological sensors modulated by their structural scaffolds? The role of the structural muscle proteins alpha-actinin-2 and alpha-actinin-3 as modulators of biological sensors. FEBS Lett. 2010;584(14):2974-2980.
4. North KN, Yang N, Wattanasirichaigoon D, Mills M, Easteal S, Beggs AH. A common nonsense mutation results in alpha-actinin-3 deficiency in the general population. Nat Genet. 1999;21(4):353-354.
5. Yang N, et al. ACTN3 genotype is associated with human elite athletic performance. Am J Hum Genet. 2003;73(3):627-631.
6. Niemi AK, Majamaa K. Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes. Eur J Hum Genet. 2005;13(8):965-969.
7. Roth SM, Walsh S, Liu D, Metter EJ, Ferrucci L, Hurley BF. The ACTN3 R577X nonsense allele is under-represented in elite-level strength athletes. Eur J Hum Genet. 2008;16(3):391-394.
8. Druzhevskaya AM, Ahmetov II, Astratenkova IV, Rogozkin VA. Association of the ACTN3 R577X polymorphism with power athlete status in Russians. Eur J Appl Physiol. 2008;103(6):631-634.
9. Papadimitriou ID, Papadopoulos C, Kouvatsi A, Triantaphyllidis C. The ACTN3 gene in elite Greek track and field athletes. Int J Sports Med. 2008;29(4):352-355.
10. Clarkson PM, et al. ACTN3 genotype is associated with increases in muscle strength in response to resistance training in women. J Appl Physiol. 2005;99(1):154-163.
11. Moran CN, et al. Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks. Eur J Hum Genet. 2007;15(1):88-93.
12. Walsh S, Liu D, Metter EJ, Ferrucci L, Roth SM. ACTN3 genotype is associated with muscle phenotypes in women across the adult age span. J Appl Physiol. 2008;105(5):1486-1491.
13. Vincent B, et al. ACTN3 (R577X) genotype is associated with fiber type distribution. Physiol Genomics. 2007;32(1):58-63.
14. Eynon N, et al. ACTN3 R577X polymorphism and Israeli top-level athletes. Int J Sports Med. 2009;30(9):695-698.
15. Eynon N, et al. The ACTN3 R577X polymorphism across three groups of elite male European athletes. PLoS ONE. 2012;7(8):e43132.
16. Pimenta EM, et al. The ACTN3 genotype in soccer players in response to acute eccentric training. Eur J Appl Physiol. 2012;112(4):1495-1503.
17. MacArthur DG, et al. Loss of ACTN3 gene function alters mouse muscle metabolism and shows evidence of positive selection in humans. Nat Genet. 2007;39(10):1261-1265.
18. MacArthur DG, et al. An Actn3 knockout mouse provides mechanistic insights into the association between α-actinin-3 deficiency and human athletic performance. Hum Mol Genet. 2008;17(8):1076-1086.
19. Quinlan KG, et al. α-Actinin-3 deficiency results in reduced glycogen phosphorylase activity and altered calcium handling in skeletal muscle. Hum Mol Genet. 2010;19(7):1335-1346.
20. Faulkner G, et al. FATZ, a filamin-, actinin-, and telethonin-binding protein of the Z-disc of skeletal muscle. J Biol Chem. 2000;275(52):41234-41242.
21. Takada F, et al. Myozenin: an alpha-actinin- and gamma-filamin-binding protein of skeletal muscle Z lines. Proc Natl Acad Sci U S A. 2001;98(4):1595-1600.
22. Frey N, Richardson JA, Olson EN. Calsarcins, a novel family of sarcomeric calcineurin-binding proteins. Proc Natl Acad Sci U S A. 2000;97(26):14632- 14637.
23. Frey N, Olson EN. Calsarcin-3, a novel skeletal muscle-specific member of the calsarcin family, interacts with multiple Z-disc proteins. J Biol Chem. 2002;277(16):13998-14004.
24. Chin ER, et al. A calcineurin-dependent transcriptional pathway controls skeletal muscle fiber type. Genes Dev. 1998;12(16):2499-2509.
25. Delling U, Tureckova J, Lim HW, De Windt LJ, Rotwein P, Molkentin JD. A calcineurin-NFATc3-dependent pathway regulates skeletal muscle differentiation and slow myosin heavy-chain expression. Mol Cell Biol. 2000;20(17):6600-6611.
26. Jiang LQ, Garcia-Roves PM, de Castro Barbosa T, Zierath JR. Constitutively active calcineurin in skeletal muscle increases endurance performance and mitochondrial respiratory capacity. Am J Physiol Endocrinol Metab. 2010;298(1):E8-E16.
27. Long YC, Glund S, Garcia-Roves PM, Zierath JR. Calcineurin regulates skeletal muscle metabolism via coordinated changes in gene expression. J Biol Chem. 2007;282(3):1607-1614.
28. Frey N, et al. Calsarcin-2 deficiency increases exercise capacity in mice through calcineurin/NFAT activation. J Clin Invest. 2008;118(11):3598-3608.
29. Kingsbury TJ, Cunningham KW. A conserved family of calcineurin regulators. Genes Dev. 2000;14(13):1595-1604.
30. Yang J, et al. Independent signals control expression of the calcineurin inhibitory proteins MCIP1 and MCIP2 in striated muscles. Circ Res. 2000;87(12):E61-E68.
31. Rothermel BA, Vega RB, Williams RS. The role of modulatory calcineurin-interacting proteins in calcineurin signaling. Trends Cardiovasc Med. 2003;13(1):15-21.
32. Dolmetsch RE, Lewis RS, Goodnow CC, Healy JI. Differential activation of transcription factors induced by Ca2+ response amplitude and duration. Nature. 1997;386(6627):855-858.
33. Mahoney DJ, Parise G, Melov S, Safdar A, Tarnopolsky MA. Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise. FASEB J. 2005;19(11):1498-1500.
34. Seto JT, et al. The effect of α-actinin-3 deficiency on muscle aging. Exp Gerontol. 2011;46(4):292-302.
35. Sloniger MA, Cureton KJ, Prior BM, Evans EM. Lower extremity muscle activation during horizontal and uphill running. J Appl Physiol. 1997;83(6):2073-2079.
36. Seto JT, et al. Deficiency of alpha-actinin-3 is associated with increased susceptibility to contraction-induced damage and skeletal muscle remodeling. Hum Mol Genet. 2011;20(15):2914-2927.
37. Lek M, Quinlan KG, North KN. The evolution of skeletal muscle performance: gene duplication and divergence of human sarcomeric alpha-actinins. Bioessays. 2010;32(1):17-25.
38. Garton F, Seto JT, North KN, Yang N. Validation of an automated computational method for skeletal muscle fibre morphometry analysis. Neuromuscul Disord. 2010;20(8):540-547.
39. Gregorevic P, et al. Systemic delivery of genes to striated muscles using adeno-associated viral vectors. Nat Med. 2004;10(8):828-834.