title: Nuclear F-actin formation and reorganization upon cell spreading.
abstract: We recently discovered signal-regulated nuclear actin network assembly. However, in contrast to cytoplasmic actin regulation, polymeric nuclear actin structures and functions remain only poorly understood. Here we describe a novel molecular tool to visualize real-time nuclear actin dynamics by targeting the Actin-Chromobody-TagGFP to the nucleus, thus establishing a nuclear Actin-Chromobody. Interestingly, we observe nuclear actin polymerization into dynamic filaments upon cell spreading and fibronectin stimulation, both of which appear to be triggered by integrin signaling. Furthermore, we show that nucleoskeletal proteins such as the LINC (linker of nucleoskeleton and cytoskeleton) complex and components of the nuclear lamina couple cell spreading or integrin activation by fibronectin to nuclear actin polymerization. Spreading-induced nuclear actin polymerization results in serum response factor (SRF)-mediated transcription through nuclear retention of myocardin-related transcription factor A (MRTF-A). Our results reveal a signaling pathway, which links integrin activation by extracellular matrix interaction to nuclear actin polymerization through the LINC complex, and therefore suggest a role for nuclear actin polymerization in the context of cellular adhesion and mechanosensing.
authors.affiliation: From the Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Plessner
authors.affiliation: From the Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Melak
authors.affiliation: From the Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany.
authors.forename: Pilar
authors.initials: P
authors.lastname: Chinchilla
authors.affiliation: From the Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Baarlink
authors.affiliation: From the Institute of Pharmacology, Biochemical-Pharmacological Center (BPC), University of Marburg, Karl-von-Frisch-Strasse 1, 35043 Marburg, Germany robert.grosse@staff.uni-marburg.de.
authors.forename: Robert
authors.initials: R
authors.lastname: Grosse
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism*; D048430:Cell Shape / Q000502:physiology*; D048429:Cell Size; D051379:Mice; D041681:NIH 3T3 Cells; D034881:Nuclear Lamina / Q000378:metabolism; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary
chemical_list: D000199:Actins
keywords: Actin; Fibronectin; Formin; Mechanotransduction; Nuclear Envelope; Nucleus