Cytoskeletal regulation of epithelial cell shape and nucleocytoskeletal coupling. (a) Actin stress fibers interact with myosin II molecular motors to form contractile actomyosin stress fibers that exert vertical (perinuclear actin fibers) or lateral (ventral actin fibers) compressive forces on the nucleus. (b) Perinuclear and ventral stress fibers interact with the nuclear lamina through LINC complexes (in orange), whereas their extremities are connected to the extracellular matrix (ECM) through focal adhesions (in red). Dorsal stress fibers do not contain myosin II and, thus, are unable to exert contractile forces, whereas transverse arcs are contractile acto-myosin bundles that are involved in the retrograde flow in migrating cells. (c) The actin cytoskeleton is organized into a belt of bundled actin filaments that runs around the apical end of the cell. (d) Tight junctions, adherens junctions, and gap junctions form an adhesion belt that encircles each of the interacting epithelial cells, while a contractile bundle of actin filaments runs along the cytoplasmic surface of the junctional plasma membrane. (e) Focal adhesions serve as a mechanotransduction hotspot to transmit forces from the ECM to the nucleus through integrins, which are transmembrane proteins connected to the cell cytoskeleton that use LINC complexes to interact with the nuclear lamina. LINC complex is a protein complex associated with both inner (INM) and outer (ONM) membranes of the nucleus that physically connect the nuclear interior with the cytoskeleton.