Affiliation:
1. Cross Cancer Institute and Department of Oncology, Faculty of Medicine, University of Alberta, Edmonton, AB T6G 1Z2, Canada.
Abstract
Actin exists as a dynamic equilibrium of monomers and polymers within the nucleus of living cells. It is utilized by the cell for many aspects of gene regulation, including mRNA processing, chromatin remodelling, and global gene expression. Polymeric actin is now specifically linked to transcription by RNA polymerase I, II, and III. An active process, requiring both actin polymers and myosin, appears to drive RNA polymerase I transcription, and is also implicated in long-range chromatin movement. This type of mechanism brings activated genes from separate chromosomal territories together, and then participates in their compartmentalization near nuclear speckles. Nuclear speckle formation requires polymeric actin, and factors promoting polymerization, such as profilin and PIP2, are concentrated there. A review of the literature shows that a functional population of G-actin cycles between the cytoplasm and the nucleoplasm. Its nuclear concentration is dependent on the cytoplasmic G-actin pool, as well as on the activity of import and export mechanisms and the availability of interactions that sequester it within the nucleus. The N-WASP-Arp2/3 actin polymer-nucleating mechanism functions in the nucleus, and its mediators, including NCK, PIP2, and Rac1, can be found in the nucleoplasm, where they likely influence the kinetics of polymer formation. The actin polymer species produced are tightly regulated, and may take on conformations not easily recognized by phalloidin. Many of the factors that cleave F-actin in the cytoplasm are present at high levels in the nucleoplasm, and are also likely to affect actin dynamics there. The absolute and relative G-actin content in the nucleoplasm and the cytoplasm of a cell contains information about the homeostatic state of that cell. We propose that the cycling of G-actin between the nucleus and cytoplasm represents a signal transduction mechanism that can function through both extremes of global cellular G-actin content. MAL signalling within the serum response factor pathway, when G-actin levels are low, represents a well-studied example of actin functioning in signal transduction. The translocation of NCK into the nucleus, along with G-actin, during dissolution of the cytoskeleton in response to DNA damage represents another instance of a unique signalling mechanism operating when G-actin levels are high.
Publisher
Canadian Science Publishing
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
116 articles.
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