Introduction that a long time ago it was a scientific breakthrough to show that actin exists at all, that it took years and years to convince truculent groups of actin pioneers that a non-muscle cell contains actin as well, that actin is not a singular and once for all invention in evolution, but is the founder of a large family of isoforms and related proteins, and that quite a number of these proteins can be found in different subcellular compartments. For example, it has been established as a regular component of both, the cytoplasm and the nucleus; but this perception is the result of a fight that went on for decades. The dawn: actin as a muscle component 1859 1887 Muscle actin comes of age 1992 2004 It is far beyond the scope of this review to cover the avalanche of actin and myosin research that started after those first molecular characterizations. Of course, muscle was and still is the major source to purify actin from, and, consequently, the research during the following decades used exclusively muscle actin. Actin conquers the cytoplasm But as it is in science, one opens one door and discovers ten closed ones. Keeping that in mind a scientist should always be suspicious regarding dogmas of all sorts. For some time it was almost a law that actin exists only in skeletal muscle and that the well-known conventional myosin is the only motor protein which turns the world go round. Today it is a common place that both assumptions were wrong, although it was quite a task to convince the scientific community. 2+ 1962 1963 1967 Physarum polycephalum 1966a b 1968 1973 1974 1981 1975 Actin as the prototype of a large family Today conventional actin is thoroughly studied, with respect to its polymerization and depolymerization equilibrium, its function in the cytoskeleton as a morphological stabilizer, its role during motile activities of a cell, its three-dimensional structure, its binding partners, etc. But the traitorous word in this sentence is “conventional”. What hides behind “conventional” actin? And what is an actin-related protein? 1 Dictyostelium discoideum D. discoideum 2005 Arabidopsis thaliana D. discoideum Fig. 1 D. discoideum 2004 left panels right Upper panels Bottom panels arrow Size bar  2 2005 3 2 2 2007 2008 J Cell Biol Fig. 2 2005 blue red upper left  Fig. 3 2006 a c top right bottom right  D. discoideum 1992 2002 2000 Coming back to actins and Arps. Is it possible that the name “actin” for all of these proteins is utterly misleading? Are we wasting time in our search for cytoskeleton-related activities just because the fold triggered a wrong name? Is the so-called actin fold another example for a successful superfamily which contains only a few proteins that play a role in the cytoskeleton, while many other members are e.g. subunits of larger protein complexes in chromatin or hexokinases or proteins with yet unknown functions? Actin-like proteins in the nucleus: the early period 1969 Physarum polycephalum 1971 1974 1975 Physarum 1971 1975 1977 Physarum 1979 1984 1984 Actin and Arps in the nucleus In the last 20 years, studies on nuclear actin became fashionable, and now a new area began which firmly established actin, its relatives and binding partners as nuclear components. Cell biologists began to understand that proteins are not necessarily confined to a single intracellular compartment. Numerous examples proved that proteins may shuttle between intracellular regions and even adopt different, compartment-specific activities. Shuttling of actin and actin-related proteins between the nucleus and the cytoplasm cannot be considered any longer as an exceptional, exotic behaviour. Drosophila The development of cell biological and immunological methods over the past 20 years, like cellular expression of flurorochrome-tagged proteins in conjunction with video microscopy, and the generation of epitope-characterized monoclonal antibodies allowed to follow actin trafficking throughout the cell and its location in the nucleus. 1981 1988 2002 1999 2005 3 2006 3 3 2004 2004 2004 2006 2002 2000 In the following paragraphs, we will briefly mention the most important tasks proposed for nuclear actins. Actin filaments and a caryoskeleton 1977 1979 1999 1979 1999 1984 Xenopus 2004 2006 2006 2006 2006 2003 2003 2004 Actin/Arps and their connection with the nuclear envelope 2003 2003 2004 2000 Actin/Arps and the nucleo-cytoplasmic traffic 2001 2004 Xenopus 2001 2001 2002 2004 2005 Actin/Arps and chromatin remodelling 2004 2004 2002 2006 2000 2004 2002 Actin/Arps and transcription 2006 2006 2006 2006 Xenopus 1984 1984 2004 2006 2004 2004 2005 Actin ligands in the nucleus 2005 1982 1988 2000 2004 2005 2003 1998 2007 2003 1999 2006 2005 Acanthamoeba 1989 1989 2000 2006 2006 Conclusions So, have we now lost the student being confronted with actin for the first time in his scientific education, or have we been able to attract his curiosity for this abundant, highly conserved, mysterious protein? 4 Fig. 4 top bottom 2008 2006 2005 2006 2005 2007 one symbol  2006