title: The reorientation of cell nucleus promotes the establishment of front-rear polarity in migrating fibroblasts.
abstract: The establishment of cell polarity is an essential step in the process of cell migration. This process requires precise spatiotemporal coordination of signaling pathways that in most cells create the typical asymmetrical profile of a polarized cell with nucleus located at the cell rear and the microtubule organizing center (MTOC) positioned between the nucleus and the leading edge. During cell polarization, nucleus rearward positioning promotes correct microtubule organizing center localization and thus the establishment of front-rear polarity and directional migration. We found that cell polarization and directional migration require also the reorientation of the nucleus. Nuclear reorientation is manifested as temporally restricted nuclear rotation that aligns the nuclear axis with the axis of cell migration. We also found that nuclear reorientation requires physical connection between the nucleus and cytoskeleton mediated by the LINC (linker of nucleoskeleton and cytoskeleton) complex. Nuclear reorientation is controlled by coordinated activity of lysophosphatidic acid (LPA)-mediated activation of GTPase Rho and the activation of integrin, FAK (focal adhesion kinase), Src, and p190RhoGAP signaling pathway. Integrin signaling is spatially induced at the leading edge as FAK and p190RhoGAP are predominantly activated or localized at this location. We suggest that integrin activation within lamellipodia defines cell front, and subsequent FAK, Src, and p190RhoGAP signaling represents the polarity signal that induces reorientation of the nucleus and thus promotes the establishment of front-rear polarity.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Miloslava
authors.initials: M
authors.lastname: Maninová
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Klímová
authors.affiliation: University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: J Thomas
authors.initials: JT
authors.lastname: Parsons
authors.affiliation: University of Virginia Health System, Charlottesville, VA, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Weber
authors.affiliation: Department of Cell Biology, Harvard Medical School, Boston, MA, USA.
authors.forename: Marcin P
authors.initials: MP
authors.lastname: Iwanicki
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Electronic address: vomy@biomed.cas.cz.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Vomastek
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D002467:Cell Nucleus / Q000378:metabolism*; D016764:Cell Polarity; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D051381:Rats; D015398:Signal Transduction
chemical_list: D003598:Cytoskeletal Proteins