Cytoskeleton: Formins Induce Nuclear Actin Assembly

RESEARCH HIGHLIGHTS

Nature Reviews Molecular Cell Biology | AOP, published online 24 April 2013; doi:10.1038/nrm3580

CYTOSKELETON nuclear export signal (NES-Dia1ct)) that formins drive actin assembly in the or constitutively active MAL. nucleus in response to serum. Moreover, they found that nuclear So, can MAL–SRF activity be induced Formins induce nuclear actin polymerization was required for upon nuclear mDia activation? Dia1ct-driven SRF activity, as Dia1ct To activate endogenous formins in actin assembly did not induce SRF activity when an the nucleus, the authors used an actin mutant that cannot polymerize optogenetic tool, whereby mDia Formins promote the assembly of actin was overexpressed in the nucleus. autoinhibition is released by the filaments in the cytoplasm. This leads Interestingly, only nuclear Dia1ct but not photoactivation of a diaphanous formins drive to the release of MAL (megakaryocytic cytoplasmic NES-Dia1ct could prevent autoregulatory domain. Indeed, acute leukaemia; also known as MRTF) the sequestration of MAL by nuclear repeated illumination of cells, and actin assembly from monomeric G-actin and the G-actin, which suggests that nuclear thus mDia activation, resulted in the in the nucleus accumulation of this cofactor, which actin polymerization releases MAL from reversible assembly of nuclear actin stimulates serum response factor G-actin. Moreover, cells expressing a filaments, MAL nuclear accumulation (SRF)-dependent expression of dominant-negative mDia mutant that and SRF activity. cytoskeletal target genes, in the localizes exclusively to the nucleus Together, these results show that nucleus. Although diaphanous-related exhibited decreased serum-induced the assembly of dynamic nuclear formins (mDia) have been detected in SRF activity compared with control cells, actin networks in response to serum is the nucleus, it was unclear whether they suggesting that nuclear mDia is required dependent on nuclear mDia activation. have a nuclear function. Now, Grosse for the serum response. Andrea Du Toit and colleagues show that activated Next, the authors assessed nuclear mDia promotes the assembly of nuclear actin assembly dynamics in ORIGINAL RESEARCH PAPER Baarlink, C., a nuclear actin network that results in cultured mammalian cells. Using an Wang, H. & Grosse, R. Nuclear actin network MAL–SRF-dependent gene expression. F-actin-specific probe fused to a nuclear assembly by formins regulates the SRF coactivator MAL. Science 4 Apr 2013 (doi:10.1126/ First, the authors showed that localization sequence (NLS) as well as science.1235038) a constitutively active version of phalloidin staining to label actin, they FURTHER READING Olson, E. N. & Nordheim, A. mammalian mDia1 (Dia1ct, which confirmed that serum rapidly induces Linking actin dynamics and gene transcription to drive cellular motile functions. Nature Rev. Mol. is predominantly nuclear) induced nuclear actin polymerization and Cell Biol. 11, 353–365 (2010) | Chesarone, M. A., SRF-dependent gene expression showed that knockdown of mammalian DuPage, A. M. & Goode, B. L. Unleashing formins to to a similar level as its cytoplasmic mDia1 and mDia2 decreased the remodel the actin and microtubule cytoskeletons. Nature Rev. Mol. Cell Biol. 11, 62–74 (2010) NPG counterpart (Dia1ct fused to a assembly rates. This supports the notion

NATURE REVIEWS | MOLECULAR CELL BIOLOGY VOLUME 14 | JUNE 2013