title: Talin Is Required Continuously for Cardiomyocyte Remodeling during Heart Growth in Drosophila.
abstract: Mechanotransduction of tension can govern the remodeling of cardiomyocytes during growth or cardiomyopathy. Tension is signaled through the integrin adhesion complexes found at muscle insertions and costameres but the relative importance of signalling during cardiomyocyte growth versus remodelling has not been assessed. Employing the Drosophila cardiomyocyte as a genetically amenable model, we depleted the levels of Talin, a central component of the integrin adhesion complex, at different stages of heart growth and remodeling. We demonstrate a continuous requirement for Talin during heart growth to maintain the one-to-one apposition of myofibril ends between cardiomyocytes. Retracted myofibrils cannot regenerate appositions to adjacent cells after restoration of normal Talin expression, and the resulting deficit reduces heart contraction and lifespan. Reduction of Talin during heart remodeling after hatching or during metamorphosis results in pervasive degeneration of cell contacts, myofibril length and number, for which restored Talin expression is insufficient for regeneration. Resultant dilated cardiomyopathy results in a fibrillating heart with poor rhythmicity. Cardiomyocytes have poor capacity to regenerate deficits in myofibril orientation and insertion, despite an ongoing capacity to remodel integrin based adhesions.
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: Simina
authors.initials: S
authors.lastname: Bogatan
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: Duygu
authors.initials: D
authors.lastname: Cevik
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Valentin
authors.initials: V
authors.lastname: Demidov
authors.affiliation: Department of Biology, Taylor University, Euler Science Complex, 236 W. Reade Ave, Upland, IN, 46989, United States of America.
authors.forename: Jessica
authors.initials: J
authors.lastname: Vanderploeg
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: Abdullah
authors.initials: A
authors.lastname: Panchbhaya
authors.affiliation: Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Vitkin
authors.affiliation: Department of Biology, McMaster University, Hamilton, ON, Canada.
authors.forename: J Roger
authors.initials: JR
authors.lastname: Jacobs
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000254:growth & development* / Q000502:physiology*; D006321:Heart / Q000254:growth & development*; D007814:Larva / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000502:physiology*; D038081:Organogenesis; D016608:Talin / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D016608:Talin