title: Nuclear actin network assembly by formins regulates the SRF coactivator MAL.
abstract: Formins are potent activators of actin filament assembly in the cytoplasm. In turn, cytoplasmic actin polymerization can promote release of actin from megakaryocytic acute leukemia (MAL) protein for serum response factor (SRF) transcriptional activity. We found that formins polymerized actin inside the mammalian nucleus to drive serum-dependent MAL-SRF activity. Serum stimulated rapid assembly of actin filaments within the nucleus in a formin-dependent manner. The endogenous formin mDia was regulated with an optogenetic tool, which allowed for photoreactive release of nuclear formin autoinhibition. Activated mDia promoted rapid and reversible nuclear actin network assembly, subsequent MAL nuclear accumulation, and SRF activity. Thus, a dynamic polymeric actin structure within the nucleus is part of the serum response.
authors.affiliation: Institute of Pharmacology, Biochemical-Pharmacological Center, University of Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Baarlink
authors.forename: Haicui
authors.initials: H
authors.lastname: Wang
authors.forename: Robert
authors.initials: R
authors.lastname: Grosse
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D000080865:Formins; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D041681:NIH 3T3 Cells; D019913:Nuclear Localization Signals / Q000378:metabolism; D058105:Polymerization; D044967:Serum / Q000378:metabolism; D026362:Serum Response Factor / Q000819:agonists*; D015534:Trans-Activators
chemical_list: D000199:Actins; D002352:Carrier Proteins; D000080865:Formins; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D009252:NADPH Dehydrogenase; D019913:Nuclear Localization Signals; D026362:Serum Response Factor; C491464:Diap1 protein, mouse; C508552:Dia2 protein, mouse; C511173:Mrtfa protein, mouse; D015534:Trans-Activators