title: FAK transduces extracellular forces that orient the mitotic spindle and control tissue morphogenesis.
abstract: Spindle orientation is critical for proper morphogenesis of organs and tissues as well as for the maintenance of tissue morphology. Although significant progress has been made in understanding the mechanisms linking the cell cortex to the spindle and the well-documented role that extracellular forces play in spindle orientation, how such forces are transduced to the cortex remains poorly understood. Here we report that focal adhesion kinase (FAK) is necessary for correct spindle orientation and as a result, indispensable for proper epithelial morphogenesis in the vertebrate embryo. We show that FAK's role in spindle orientation is dependent on its ability to localize at focal adhesions and its interaction with paxillin, but is kinase activity independent. Finally, we present evidence that FAK is required for external force-induced spindle reorientation, suggesting that FAK's involvement in this process stems from a role in the transduction of external forces to the cell cortex.
authors.affiliation: Laboratory of Developmental Biology and BioImaging, Department of Biological Sciences, University of Cyprus, University Ave 1, Nicosia 2109, Cyprus.
authors.forename: Nicoletta I
authors.initials: NI
authors.lastname: Petridou
authors.affiliation: Laboratory of Developmental Biology and BioImaging, Department of Biological Sciences, University of Cyprus, University Ave 1, Nicosia 2109, Cyprus.
authors.forename: Paris A
authors.initials: PA
authors.lastname: Skourides
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002448:Cell Adhesion; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000254:growth & development / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005110:Extracellular Space / Q000502:physiology*; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000737:chemistry / Q000172:deficiency / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008677:Metaphase; D051379:Mice; D009024:Morphogenesis; D051419:Paxillin / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism*; D013329:Structure-Activity Relationship; D059008:Time-Lapse Imaging; D014981:Xenopus
chemical_list: D051419:Paxillin; D051416:Focal Adhesion Protein-Tyrosine Kinases