title: How does α-actinin-3 deficiency alter muscle function? Mechanistic insights into ACTN3, the 'gene for speed'.
abstract: An estimated 1.5 billion people worldwide are deficient in the skeletal muscle protein α-actinin-3 due to homozygosity for the common ACTN3 R577X polymorphism. α-Actinin-3 deficiency influences muscle performance in elite athletes and the general population. The sarcomeric α-actinins were originally characterised as scaffold proteins at the muscle Z-line. Through studying the Actn3 knockout mouse and α-actinin-3 deficient humans, significant progress has been made in understanding how ACTN3 genotype alters muscle function, leading to an appreciation of the diverse roles that α-actinins play in muscle. The α-actinins interact with a number of partner proteins, which broadly fall into three biological pathways-structural, metabolic and signalling. Differences in functioning of these pathways have been identified in α-actinin-3 deficient muscle that together contributes to altered muscle performance in mice and humans. Here we discuss new insights that have been made in understanding the molecular mechanisms that underlie the consequences of α-actinin-3 deficiency.
authors.affiliation: The Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, NSW 2145, Australia; Discipline of Paediatrics and Child Health, Faculty of Medicine, The University of Sydney, NSW 2006, Australia.
authors.forename: Fiona X Z
authors.initials: FX
authors.lastname: Lee
authors.affiliation: Murdoch Childrens Research Institute, the Royal Children's Hospital, VIC 3052, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Houweling
authors.affiliation: The Institute for Neuroscience and Muscle Research, The Children's Hospital at Westmead, NSW 2145, Australia; Murdoch Childrens Research Institute, the Royal Children's Hospital, VIC 3052, Australia.
authors.forename: Kathryn N
authors.initials: KN
authors.lastname: North
authors.affiliation: Discipline of Paediatrics and Child Health, Faculty of Medicine, The University of Sydney, NSW 2006, Australia; School of Biotechnology and Biomolecular Sciences, University of New South Wales, NSW 2052, Australia. Electronic address: kate.quinlan@unsw.edu.au.
authors.forename: Kate G R
authors.initials: KG
authors.lastname: Quinlan
mesh_terms: D000185:Actinin / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D054874:Athletic Performance / Q000502:physiology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D009135:Muscular Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C118456:ACTN3 protein, human; D000185:Actinin
keywords: Athletic performance; Common human polymorphism; Molecular mechanism; Muscle function; Protein interactions; α-Actinin-3 deficiency