Disease relevance of ACTN3

• Deficiency of alpha-actinin-3 (ACTN3) occurs in different forms of muscular dystrophy [1].
• Three alpha-actinin-3-deficient patients had pure CMD and presented in the newborn period with muscle weakness, hypotonia and arthrogryposis [2].

High impact information on ACTN3

• The absence of a disease phenotype secondary to alpha-actinin-3 deficiency is likely due to compensation by the homologous protein, alpha-actinin-2 [3].
• We have recently demonstrated that the skeletal-muscle actin-binding protein alpha-actinin-3 is absent in 18% of healthy white individuals because of homozygosity for a common stop-codon polymorphism in the ACTN3 gene, R577X. alpha-Actinin-3 is specifically expressed in fast-twitch myofibers responsible for generating force at high velocity [3].
• We are currently exploring the function and evolutionary history of the ACTN3 gene and other alpha-actinin family members [4].
• We report the crystal structure of the actin binding domain of human muscle alpha-actinin-3, which is formed by two consecutive calponin homology domains arranged in a "closed" conformation [5].
• Association analysis of the ACTN3 R577X polymorphism and complex quantitative body composition and performance phenotypes in adolescent Greeks [6].

Biological context of ACTN3

• As with other muscle-specific isoforms, the EF-hand domains in ACTN2 and ACTN3 are predicted to be incapable of binding calcium, suggesting that actin binding is not calcium sensitive [7].
• ACTN2 was mapped to human chromosome 1q42-q43 and ACTN3 to 11q13-q14 by somatic cell hybrid panels and fluorescent in situ hybridization [7].
• Mitochondrial DNA and ACTN3 genotypes in Finnish elite endurance and sprint athletes [8].
• We found no association between ACTN3 R577X genotype and muscle phenotype in men [9].
• However, women homozygous for the ACTN3 577X allele (XX) had lower baseline MVC compared with heterozygotes (P < 0.05) when adjusted for body mass and age [9].

Anatomical context of ACTN3

• Northern blot analysis demonstrated that ACTN2 is expressed in both skeletal and cardiac muscle, but ACTN3 expression is limited to skeletal muscle [7].
• We studied expression of the skeletal muscle isoforms of alpha-actinin (alpha-actinin-2 and alpha-actinin-3) in muscle biopsies from 12 patients with pure CMD (including one with a merosin abnormality), two with unclassified CMD and central nervous system (CNS) involvement, and three with other neuromuscular disorders [2].
• We report the analysis of muscle type composition on m. vastus lateralis from six endurance athletes through the expression of fast, slow, and developmental myosin isoforms, and alpha-actinin-3 (ACTN3) protein [10].

Associations of ACTN3 with chemical compounds

• ACTN3 Genotype in Professional Endurance Cyclists [11].

Other interactions of ACTN3

• ACTN3 and MLCK genotype associations with exertional muscle damage [12].
• We have thus undertaken fine-scale mapping of a 3.2-Mb region flanked by ACTN3 and FGF3 [13].
• Layer-specific differential expression was validated at both mRNA and protein level for MYH3, MYH6, and ACTN3 [14].

Analytical, diagnostic and therapeutic context of ACTN3

• Four specimens exhibited deficient alpha-actinin-3 staining by immunofluorescence and/or Western blot analysis [2].

References