title: Emerin organizes actin flow for nuclear movement and centrosome orientation in migrating fibroblasts.
abstract: In migrating fibroblasts, rearward movement of the nucleus orients the centrosome toward the leading edge. Nuclear movement results from coupling rearward-moving, dorsal actin cables to the nucleus by linear arrays of nesprin-2G and SUN2, termed transmembrane actin-associated nuclear (TAN) lines. A-type lamins anchor TAN lines, prompting us to test whether emerin, a nuclear membrane protein that interacts with lamins and TAN line proteins, contributes to nuclear movement. In fibroblasts depleted of emerin, nuclei moved nondirectionally or completely failed to move. Consistent with these nuclear movement defects, dorsal actin cable flow was nondirectional in cells lacking emerin. TAN lines formed normally in cells lacking emerin and were coordinated with the erratic nuclear movements, although in 20% of the cases, TAN lines slipped over immobile nuclei. Myosin II drives actin flow, and depletion of myosin IIB, but not myosin IIA, showed similar nondirectional nuclear movement and actin flow as in emerin-depleted cells. Myosin IIB specifically coimmunoprecipitated with emerin, and emerin depletion prevented myosin IIB localization near nuclei. These results show that emerin functions with myosin IIB to polarize actin flow and nuclear movement in fibroblasts, suggesting a novel function for the nuclear envelope in organizing directional actin flow and cytoplasmic polarity.
authors.affiliation: Department of Pathology and Cell Biology, Columbia University, New York, NY 10032 Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
authors.forename: Wakam
authors.initials: W
authors.lastname: Chang
authors.forename: Eric S
authors.initials: ES
authors.lastname: Folker
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Worman
authors.forename: Gregg G
authors.initials: GG
authors.lastname: Gundersen
mesh_terms: D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000235:genetics; D000818:Animals; D002460:Cell Line; D002465:Cell Movement / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D016764:Cell Polarity / Q000235:genetics* / Q000502:physiology; D005347:Fibroblasts; D049452:Green Fluorescent Proteins / Q000235:genetics; D034882:Lamins / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics; D024501:Nonmuscle Myosin Type IIB / Q000235:genetics* / Q000378:metabolism; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics*; D034622:RNA Interference; D034741:RNA, Small Interfering; D034501:Telomere-Binding Proteins / Q000235:genetics
chemical_list: D034882:Lamins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; C520338:Sun2 protein, mouse; C485903:Syne2 protein, mouse; D034501:Telomere-Binding Proteins; C092710:emerin; D049452:Green Fluorescent Proteins; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB