Actin in the nucleus: what form and what for?

We warmly dedicate this paper to the memory of Nils Ringertz whom we both knew and admired as a leading cell biologist of the nucleus but who also, in his senior career, advanced the entire estate and legacy of biomedical science.
https://doi.org/10.1016/S1047-8477(02)00528-2Get rights and content

Abstract

Actin is an abundant protein in most nonmuscle cells. It has often been observed in isolated nuclei, yet cytoplasmic contamination was of course initially regarded as the most plausible origin. Numerous studies on nuclear actin appeared in the 1970s and 1980s, but the picture remained rather muddy. The viewpoint at that time was that actin—shown to move freely between cytoplasm and nucleus—was a mere “thermodynamic wanderer,” transiently occupying the nucleus. More recently, evidence has been mounting that actin’s presence in the nucleus is not simply governed by the laws of diffusion. The same holds true for the finding of various actin-related proteins in the nucleus, and the case for nuclear myosin, specifically myosin I, is now quite convincing. Moreover, the first intimations of functional roles of nuclear actin are now emerging. Here we examine the overall subject from cell biological and chemical perspectives. The major issue is no longer the presence of actin in the nucleus but rather its supramolecular organization, intranuclear locations, and, of course, functions. These issues interface with recent findings that reveal a surprisingly diverse repertoire of actin conformations and oligomer and polymer forms beyond monomeric G-actin and polymeric F-actin. We present ideas for advancing the nuclear actin field and call for a renewed attack on this major problem in cell biology.

Section snippets

Prelude

The following insightful (then and now) comment was made by Max Alfert, a cytologist at the University of California, Berkeley, at a symposium on “The Chemical Basis of Heredity” held at Johns Hopkins University in 1956. His comment followed a talk on chromosome structure by Hans Ris (University of Wisconsin).

Dr. Bernard Nebel at the Argonne laboratory has had an ingenious idea to get at the submicroscopic structure of nuclear material. This has just been reported at Cold Spring Harbor and is

A shift in perspective

While some of these studies were appearing, new work was underway on possible functional roles of nuclear actin. In these studies the bona fide nuclear presence of actin is essentially taken for granted and it is the results from functional assays of known nuclear processes that are given due weight. For example, nuclear actin has been implicated in chromatin remodeling and gene activation via a family of nuclear proteins called BAFs, which can be isolated from nuclei in association with an

The diverse repertoire of actin oligomers, polymers, and crystals

A provocative and potentially underappreciated finding as regards the state of nuclear actin was the report of Gonsior et al. (1999) that the immunochemical signature of nuclear actin is different from that of cytoplasmic actin in mammalian cells. Historically, classical F-actin has been envisioned as being relatively long and unbranched. However, more detailed thermodynamic studies have revealed that short actin filaments are metastable relative to long ones, because at these short lengths an

Avenues for future research

Viewing all the information and integrating it with our experience and present instincts, we envision four avenues of research that lie before us.

1. Increased investigation of the presence of actin, myosin, Arp’s, and actin-associating proteins in the nucleus.

It will be important to continue to validate the nuclear presence of actin, myosin, and Arp’s and actin-associating proteins. However, the present evidence is sufficiently persuasive so that critical scrutiny should be reserved for claims

Conclusion

We have presented here our current perspectives on nuclear actin and nuclear actin-associating proteins as we see this rather embryonic field at present. Our purpose in this article is to convey our conviction about the reality of nuclear actin on the one hand but, even more emphatically, our enthusiasm for a productive future of this idea in cell biology. In this spirit, we hope that our article will mobilize colleagues to pursue and enrich our understanding of nuclear actin.

We have emphasized

An epilogue for the next generation

The lives of Wladimir Engelhardt (left) and Albert Szent-Gyorgyi (right) were in close temporal synchrony. Neither could have known that their beloved actin, myosin, and actomyosin might operate beyond the sarcomere. Both of them endured intense scientific opposition and political adversity all throughout their lives. We encourage our readers, especially young ones, to remember those who went before and to take inspiration from Wladimir’s and Albert’s persistence against all odds. Persistence

Acknowledgements

This article grew out of delightfully co-catalytic discussions between the authors at the EMBO Workshop on the Functional Organization of the Cell Nucleus in Prague, April 17–19, 2002. We are grateful to Cora-Ann Schoenenberger (M.E. Müller Institute for Structural Biology, Basel) for her very helpful critical comments on a draft of the manuscript and for her major scientific role in the investigation of new actin conformations. We thank Andrew Szent-Gyorgyi (Brandeis University) and Jonathan

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