title: The Effects of Disease Models of Nuclear Actin Polymerization on the Nucleus.
abstract: Actin plays a crucial role in regulating multiple processes within the nucleus, including transcription and chromatin organization. However, the polymerization state of nuclear actin remains controversial, and there is no evidence for persistent actin filaments in a normal interphase nucleus. Further, several disease pathologies are characterized by polymerization of nuclear actin into stable filaments or rods. These include filaments that stain with phalloidin, resulting from point mutations in skeletal α-actin, detected in the human skeletal disease intranuclear rod myopathy, and cofilin/actin rods that form in response to cellular stressors like heatshock. To further elucidate the effects of these pathological actin structures, we examined the nucleus in both cell culture models as well as isolated human tissues. We find these actin structures alter the distribution of both RNA polymerase II and chromatin. Our data suggest that nuclear actin filaments result in disruption of nuclear organization, which may contribute to the disease pathology.
authors: Department of Physiology and Biophysics, University of Illinois at Chicago Chicago, IL, USA.
authors: Leonid A
authors: LA
authors: Serebryannyy
authors: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at WestmeadSydney, NSW, Australia; Faculty of Medicine, Discipline of Pediatrics and Child Health, University of SydneySydney, NSW, Australia.
authors: Michaela
authors: M
authors: Yuen
authors: Department of Physiology and Biophysics, University of Illinois at Chicago Chicago, IL, USA.
authors: Megan
authors: M
authors: Parilla
authors: Institute for Neuroscience and Muscle Research, Kids Research Institute, The Children's Hospital at WestmeadSydney, NSW, Australia; Faculty of Medicine, Discipline of Pediatrics and Child Health, University of SydneySydney, NSW, Australia.
authors: Sandra T
authors: ST
authors: Cooper
authors: Department of Physiology and Biophysics, University of Illinois at Chicago Chicago, IL, USA.
authors: Primal
authors: P
authors: de Lanerolle
keywords: RNA polymerase II; chromatin; cofilin rods; intranuclear rod myopathy; nuclear actin; nuclear filaments; nuclear structure; skeletal actin mutations