Nuclear actin and myosins in adenovirus infection

Adenovirus serotypes have been shown to cause drastic changes in nuclear organization, including the transcription machinery, during infection. This ability of adenovirus to subvert transcription in the host cell facilitates viral replication. Because nuclear actin and nuclear myosin I, myosin V and myosin VI have been implicated as direct regulators of transcription and important factors in the replication of other viruses, we sought to determine how nuclear actin and myosins are involved in adenovirus infection. We first confirmed reorganization of the host's transcription machinery to viral replication centers. We found that nuclear actin also reorganizes to sites of transcription through the intermediate but not the advanced late phase of viral infection. Furthermore, nuclear myosin I localized with nuclear actin and sites of transcription in viral replication centers. Intriguingly, nuclear myosins V and VI, which also reorganized to viral replication centers, exhibited different localization patterns, suggesting specialized roles for these nuclear myosins. Finally, we assessed the role of actin in adenovirus infection and found both cytoplasmic and nuclear actin likely play roles in adenovirus infection and replication. Together our data suggest the involvement of actin and multiple myosins in the nuclear replication and late viral gene expression of adenovirus.Fil: Fuchsova, Beata. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Instituto de Investigaciones Biotecnológicas ; Argentina. University of Illinois; Estados UnidosFil: Serebryannyy, Leonid A.. University of Illinois; Estados UnidosFil: De Lanerolle, Primal. University of Illinois; Estados Unido

Characterizing the Functional Importance of Actin Dynamics in the Nucleus

Cytoskeletal actin is a well-established regulator of cell shape and movement. Actin is also actively imported into the nucleus, where it is directly implicated in transcriptional regulation. Yet, how nuclear actin functions is unclear. Unlike cytoskeletal actin, which polymerizes into filaments, there are no visible actin filaments in the nucleus. More so, controversy still surrounds the polymerization state and dynamics of nuclear actin. Here, we explore the functional role of actin in the nucleus and the effects of changing nuclear actin’s polymerization state. Specifically, we investigate how disrupting nuclear actin dynamics by forming nuclear actin filaments impacts transcription, nuclear organization, chromatin remodeling and class I HDAC activity, as well as the contribution of nuclear actin polymerization to the pathogenesis of intranuclear rod myopathy, cellular stress, and adenovirus infection

Nuclear actin and myosins: Life without filaments

Actin and myosin are major components of the cell cytoskeleton, with structural and regulatory functions that impact many essential cellular processes. Actin and myosin were traditionally thought to function only in the cytoplasm. However, it is now well accepted that actin and multiple myosins are found in the nucleus. Increasing evidence on their functional roles has highlighted the importance of these proteins in the nuclear compartment

Nuclear Actin and Myosins: Life Without Filmaents

Actin and myosin are major components of the cell cytoskeleton, with structural and regulatory functions that impact many essential cellular processes. Actin and myosin were traditionally thought to function only in the cytoplasm. However, it is now well accepted that actin and multiple myosins are found in the nucleus. Increasing evidence on their functional roles has highlighted the importance of these proteins in the nuclear compartment

Activation of endoplasmic reticulum stress in premature aging via the inner nuclear membrane protein SUN2

Summary: One of the major cellular mechanisms to ensure cellular protein homeostasis is the endoplasmic reticulum (ER) stress response. This pathway is triggered by accumulation of misfolded proteins in the ER lumen. The ER stress response is also activated in the premature aging disease Hutchinson-Gilford progeria syndrome (HGPS). Here, we explore the mechanism of activation of the ER stress response in HGPS. We find that aggregation of the diseases-causing progerin protein at the nuclear envelope triggers ER stress. Induction of ER stress is dependent on the inner nuclear membrane protein SUN2 and its ability to cluster in the nuclear membrane. Our observations suggest that the presence of nucleoplasmic protein aggregates can be sensed, and signaled to the ER lumen, via clustering of SUN2. These results identify a mechanism of communication between the nucleus and the ER and provide insight into the molecular disease mechanisms of HGPS

The Effects of Disease Models of Nuclear Actin Polymerization on the Nucleus

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