title: SUN proteins facilitate the removal of membranes from chromatin during nuclear envelope breakdown.
abstract: SUN proteins reside in the inner nuclear membrane and form complexes with KASH proteins of the outer nuclear membrane that connect the nuclear envelope (NE) to the cytoskeleton. These complexes have well-established functions in nuclear anchorage and migration in interphase, but little is known about their involvement in mitotic processes. Our analysis demonstrates that simultaneous depletion of human SUN1 and SUN2 delayed removal of membranes from chromatin during NE breakdown (NEBD) and impaired the formation of prophase NE invaginations (PNEIs), similar to microtubule depolymerization or down-regulation of the dynein cofactors NudE/EL. In addition, overexpression of dominant-negative SUN and KASH constructs reduced the occurrence of PNEI, indicating a requirement for functional SUN-KASH complexes in NE remodeling. Codepletion of SUN1/2 slowed cell proliferation and resulted in an accumulation of morphologically defective and disoriented mitotic spindles. Quantification of mitotic timing revealed a delay between NEBD and chromatin separation, indicating a role of SUN proteins in bipolar spindle assembly and mitotic progression.
authors.affiliation: Institute of Biochemistry, Department of Biology, and 2 Light Microscopy Center, Swiss Federal Institute of Technology Zurich, CH-8093 Zurich, Switzerland.
authors.forename: Yagmur
authors.initials: Y
authors.lastname: Turgay
authors.forename: Lysie
authors.initials: L
authors.lastname: Champion
authors.forename: Csaba
authors.initials: C
authors.lastname: Balazs
authors.forename: Michael
authors.initials: M
authors.lastname: Held
authors.forename: Alberto
authors.initials: A
authors.lastname: Toso
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Gerlich
authors.forename: Patrick
authors.initials: P
authors.lastname: Meraldi
authors.forename: Ulrike
authors.initials: U
authors.lastname: Kutay
mesh_terms: D002352:Carrier Proteins / Q000378:metabolism; D049109:Cell Proliferation; D002843:Chromatin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D007700:Kinetics; D008565:Membrane Proteins / Q000502:physiology*; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000502:physiology*; D011418:Prophase; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure; D059008:Time-Lapse Imaging
chemical_list: C561542:BICD2 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; D009687:Nuclear Proteins; C506117:SUN1 protein, human; C413025:SUN2 protein, human