title: The Drosophila muscle LIM protein, Mlp84B, is essential for cardiac function.
abstract: Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP has been proposed to be a key player in the stretch-sensing response, but the molecular mechanisms underlying its function in normal and diseased cardiac muscle have not been established. A Drosophila homolog, Mlp84B, displays a similar subcellular localization at the Z-disc of sarcomeres throughout development and in the adult, suggesting Drosophila as a model to study MLP function. Here we employed genetic ablation and cardiac-specific RNA interference (RNAi) knockdown of mlp84B to investigate its role in heart function. We found that Mlp84B-deficient or heart-specific RNAi knockdown flies exhibit diastolic interval prolongation, heart rhythm abnormalities and a reduced lifespan, while showing no obvious structural phenotype. Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy.
authors: Development and Aging Program, Neuroscience, Aging and Stem Cell Research Center, Burnham Institute for Medical Research, La Jolla, CA 92037, USA.
authors: Annabelle
authors: A
authors: Mery
authors: Ouarda
authors: O
authors: Taghli-Lamallem
authors: Kathleen A
authors: KA
authors: Clark
authors: Mary C
authors: MC
authors: Beckerle
authors: Xiushan
authors: X
authors: Wu
authors: Karen
authors: K
authors: Ocorr
authors: Rolf
authors: R
authors: Bodmer
mesh_terms: D000185:Actinin / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D003971:Diastole; D029721:Drosophila Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000196:embryology / Q000378:metabolism*; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D006321:Heart / Q000196:embryology / Q000502:physiology*; D060588:LIM Domain Proteins; D008136:Longevity; D008969:Molecular Sequence Data; D009026:Mortality; D009124:Muscle Proteins / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009210:Myofibrils / Q000378:metabolism; D009928:Organ Specificity; D021381:Protein Transport; D012518:Sarcomeres / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D060588:LIM Domain Proteins; C101416:Mlp84B protein, Drosophila; D009124:Muscle Proteins; C090114:cysteine and glycine-rich protein 3; D000185:Actinin