title: Focal adhesions control cleavage furrow shape and spindle tilt during mitosis.
abstract: The geometry of the cleavage furrow during mitosis is often asymmetric in vivo and plays a critical role in stem cell differentiation and the relative positioning of daughter cells during development. Early observations of adhesive cell lines revealed asymmetry in the shape of the cleavage furrow, where the bottom (i.e., substrate attached side) of the cleavage furrow ingressed less than the top (i.e., unattached side). This data suggested substrate attachment could be regulating furrow ingression. Here we report a population of mitotic focal adhesions (FAs) controls the symmetry of the cleavage furrow. In single HeLa cells, stronger adhesion to the substrate directed less ingression from the bottom of the cell through a pathway including paxillin, focal adhesion kinase (FAK) and vinculin. Cell-cell contacts also direct ingression of the cleavage furrow in coordination with FAs in epithelial cells-MDCK-within monolayers and polarized cysts. In addition, mitotic FAs established 3D orientation of the mitotic spindle and the relative positioning of mother and daughter centrosomes. Therefore, our data reveals mitotic FAs as a key link between mitotic cell shape and spindle orientation, and may have important implications in our understanding stem cell homeostasis and tumorigenesis.
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Nilay
authors.initials: N
authors.lastname: Taneja
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Aidan M
authors.initials: AM
authors.lastname: Fenix
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Rathbun
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Millis
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Tyska
authors.affiliation: Department of Cell and Developmental Biology, SUNY Upstate Medical University, Syracuse, NY 13210, USA.
authors.forename: Heidi
authors.initials: H
authors.lastname: Hehnly
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors.forename: Dylan T
authors.initials: DT
authors.lastname: Burnette
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D048430:Cell Shape / Q000235:genetics*; D018385:Centrosome / Q000378:metabolism; D004285:Dogs; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000235:genetics; D022001:Focal Adhesions / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D008938:Mitosis / Q000235:genetics*; D008941:Spindle Apparatus / Q000235:genetics*; D016596:Vinculin / Q000235:genetics
chemical_list: D016596:Vinculin; D051416:Focal Adhesion Protein-Tyrosine Kinases