Abstract
Intranuclear rods are aggregates consisting of actin and cofilin that are formed in the nucleus in consequence of chemical or mechanical stress conditions. The formation of rods is implicated in a variety of pathological conditions, such as certain myopathies and some neurological disorders. It is still not well understood what exactly triggers the formation of intranuclear rods, whether other proteins are involved, and what the underlying mechanisms of rod assembly or disassembly are. In this study, Dictyostelium discoideum was used to examine appearance, stages of assembly, composition, stability, and dismantling of rods. Our data show that intranuclear rods, in addition to actin and cofilin, are composed of a distinct set of other proteins comprising actin-interacting protein 1 (Aip1), coronin (CorA), filactin (Fia), and the 34 kDa actin-bundling protein B (AbpB). A finely tuned spatio-temporal pattern of protein recruitment was found during formation of rods. Aip1 is important for the final state of rod compaction indicating that Aip1 plays a major role in shaping the intranuclear rods. In the absence of both Aip1 and CorA, rods are not formed in the nucleus, suggesting that a sufficient supply of monomeric actin is a prerequisite for rod formation.
Highlights
The exact protein composition of the rods and the mechanisms that trigger their formation is unclear
Short, needle-like actin-cofilin aggregates were detectable in the cytoplasm, and after 5 min of DMSO treatment these short assemblies disappeared from the cytoplasm, and rods started to aggregate inside the nucleus adjacent to the inner nuclear membrane
The results showed that rods are composed of actin and cofilin, and confirmed the presence of CorA, Aip[1], actin-bundling protein B (AbpB) and Fia whereas other actin-binding or cytoskeleton-associated proteins were not detectable in intranuclear actin rods (Table 1)
Summary
The exact protein composition of the rods and the mechanisms that trigger their formation is unclear. Especially cofilin as an actin-associated protein has been identified in DMSO-induced nuclear actin rods[15,16]. Cofilin is a protein located primarily in the cytoplasm, it translocates into the nucleus together with actin in response to various stress conditions. The functional roles of cofilin-actin rods in the nucleus remain to be elucidated, but the general assumption is that the formation of nuclear rods constitutes an option to reduce energy consumption due to a shut-off of actin-treadmilling, and provides a protective mechanism for the cell. In addition to actin and cofilin further proteins were identified as constituents of intranuclear rods including actin-interacting protein 1 (Aip1), coronin (CorA), 34-kDa actin-bundling protein B (AbpB), and filactin (Fia). Correspondence and requests for materials should be addressed to A.M.T. (email: amueller@lrz. uni-muenchen.de) www.nature.com/scientificreports/
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