title: Tight coupling between nucleus and cell migration through the perinuclear actin cap.
abstract: Although eukaryotic cells are known to alternate between 'advancing' episodes of fast and persistent movement and 'hesitation' episodes of low speed and low persistence, the molecular mechanism that controls the dynamic changes in morphology, speed and persistence of eukaryotic migratory cells remains unclear. Here, we show that the movement of the interphase nucleus during random cell migration switches intermittently between two distinct modes - rotation and translocation - that follow with high fidelity the sequential rounded and elongated morphologies of the nucleus and cell body, respectively. Nuclear rotation and translocation mediate the stop-and-go motion of the cell through the dynamic formation and dissolution, respectively, of the contractile perinuclear actin cap, which is dynamically coupled to the nuclear lamina and the nuclear envelope through LINC complexes. A persistent cell movement and nuclear translocation driven by the actin cap are halted following the disruption of the actin cap, which in turn allows the cell to repolarize for its next persistent move owing to nuclear rotation mediated by cytoplasmic dynein light intermediate chain 2.
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA narrkim@jhu.edu wirtz@jhu.edu.
authors.forename: Dong-Hwee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA.
authors.forename: Sangkyun
authors.initials: S
authors.lastname: Cho
authors.affiliation: Johns Hopkins Physical Sciences - Oncology Center, The Johns Hopkins University, Baltimore, MD 21218, USA Department of Chemical and Biomolecular Engineering, The Johns Hopkins University, Baltimore, MD 21218, USA Departments of Pathology and Oncology and Sydney Kimmel Comprehensive Cancer Center, The Johns Hopkins School of Medicine, Baltimore, MD 21205, USA narrkim@jhu.edu wirtz@jhu.edu.
authors.forename: Denis
authors.initials: D
authors.lastname: Wirtz
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D053144:Cell Nucleus Shape / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000502:physiology*; D007399:Interphase / Q000235:genetics; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D011940:Receptor Aggregation / Q000235:genetics; D012399:Rotation
chemical_list: D034904:Lamin Type A; D034741:RNA, Small Interfering; D056445:Cytoplasmic Dyneins; C548808:DYNC1LI2 protein, human
keywords: Actin cap; Cell migration; Nuclear migration