title: NRIP is newly identified as a Z-disc protein, activating calmodulin signaling for skeletal muscle contraction and regeneration.
abstract: Nuclear receptor interaction protein (NRIP, also known as DCAF6 and IQWD1) is a Ca(2+)-dependent calmodulin-binding protein. In this study, we newly identify NRIP as a Z-disc protein in skeletal muscle. NRIP-knockout mice were generated and found to have reduced muscle strength, susceptibility to fatigue and impaired adaptive exercise performance. The mechanisms of NRIP-regulated muscle contraction depend on NRIP being downstream of Ca(2+) signaling, where it stimulates activation of both 'calcineurin-nuclear factor of activated T-cells, cytoplasmic 1' (CaN-NFATc1; also known as NFATC1) and calmodulin-dependent protein kinase II (CaMKII) through interaction with calmodulin (CaM), resulting in the induction of mitochondrial activity and the expression of genes encoding the slow class of myosin, and in the regulation of Ca(2+) homeostasis through the internal Ca(2+) stores of the sarcoplasmic reticulum. Moreover, NRIP-knockout mice have a delayed regenerative capacity. The amount of NRIP can be enhanced after muscle injury and is responsible for muscle regeneration, which is associated with the increased expression of myogenin, desmin and embryonic myosin heavy chain during myogenesis, as well as for myotube formation. In conclusion, NRIP is a novel Z-disc protein that is important for skeletal muscle strength and regenerative capacity.
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Hsin-Hsiung
authors.initials: HH
authors.lastname: Chen
authors.affiliation: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Wen-Pin
authors.initials: WP
authors.lastname: Chen
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Wan-Lun
authors.initials: WL
authors.lastname: Yan
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Yuan-Chun
authors.initials: YC
authors.lastname: Huang
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Szu-Wei
authors.initials: SW
authors.lastname: Chang
authors.affiliation: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
authors.affiliation: Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: Ming-Jai
authors.initials: MJ
authors.lastname: Su
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei 100, Taiwan.
authors.forename: I-Shing
authors.initials: IS
authors.lastname: Yu
authors.affiliation: Department of Microbiology, Immunology and Biopharmaceuticals, National Chiayi University, Chiayi 600-04, Taiwan.
authors.forename: Tzung-Chieh
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yan
authors.affiliation: Department of Ophthalmology, Mackay Memorial Hospital, Taipei 104, Taiwan.
authors.forename: Yeou-Ping
authors.initials: YP
authors.lastname: Tsao
authors.affiliation: Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei 100, Taiwan showlic@ntu.edu.tw.
authors.forename: Show-Li
authors.initials: SL
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D002147:Calmodulin / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000502:physiology; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D009687:Nuclear Proteins / Q000378:metabolism*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002147:Calmodulin; D009687:Nuclear Proteins
keywords: CaM; Muscle contraction; NRIP; Regeneration; Z-disc