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

Leonid A Serebryannyy,Primal De Lanerolle,Michaela Yuen,Megan Parilla,Sandra T Cooper

doi:10.3389/fphys.2016.00454

Leonid A Serebryannyy, Primal De Lanerolle + Show 3 more

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https://doi.org/10.3389/fphys.2016.00454

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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.

Highlights

Actin is necessary for maintaining cell structure and driving cell movement and contraction (Dominguez and Holmes, 2011)
Using cofilin/actin rods and models of intranuclear rod myopathy, we find nuclear actin structures are able to change the localization of RNAPII and chromatin, potentially contributing to their pathogenesis
We found heatshock performed in Dulbecco’s phosphate-buffered saline (PBS) lacking fetal bovine serum and supplemented with CaCl2 (0.9 mM) and MgCl2 (0.5 mM) resulted in a population of cells with nuclear filaments that stained with phalloidin and incorporated cofilin (Figure 2A) as well as neighboring populations that exhibited only cofilin/actin rods or phalloidinstainable filaments but not both (Figure 2B)

Summary

Introduction

Actin is necessary for maintaining cell structure and driving cell movement and contraction (Dominguez and Holmes, 2011). The capacity of actin to be both a structural protein and generate force comes from actin’s ability to dynamically polymerize and depolymerize into polymers and filaments of different lengths. Actin translocates into the nucleus (de Lanerolle and Serebryannyy, 2011; Dopie et al, 2012). Studies suggest nuclear actin exists as monomers and highly dynamic polymers (McDonald et al, 2006).

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