title: Lamins position the nuclear pores and centrosomes by modulating dynein.
abstract: Lamins, the type V nuclear intermediate filament proteins, are reported to function in both interphase and mitosis. For example, lamin deletion in various cell types can lead to an uneven distribution of the nuclear pore complexes (NPCs) in the interphase nuclear envelope, whereas deletion of B-type lamins results in spindle orientation defects in mitotic neural progenitor cells. How lamins regulate these functions is unknown. Using mouse cells deleted of different combinations or all lamins, we show that lamins are required to prevent the aggregation of NPCs in the nuclear envelope near centrosomes in late G2 and prophase. This asymmetric NPC distribution in the absence of lamins is caused by dynein forces acting on NPCs via the dynein adaptor BICD2. We further show that asymmetric NPC distribution upon lamin depletion disrupts the distribution of BICD2 and p150 dynactin on the nuclear envelope at prophase, which results in inefficient dynein-driven centrosome separation during prophase. Therefore lamins regulate microtubule-based motor forces in vivo to ensure proper NPC distribution in interphase and centrosome separation in the mitotic prophase.
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218; Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218.
authors.forename: Yuxuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218; Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 zheng@ciwemb.edu.
authors.forename: Yixian
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D004398:Dyneins / Q000378:metabolism*; D034882:Lamins / Q000378:metabolism*; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008938:Mitosis; D009685:Nuclear Envelope / Q000378:metabolism; D022022:Nuclear Pore / Q000378:metabolism*; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: C435206:Bicd2 protein, mouse; D034882:Lamins; D008869:Microtubule-Associated Proteins; D004398:Dyneins