title: Developmental control of nuclear size and shape by Kugelkern and Kurzkern.
abstract: BACKGROUND
  The shape of a nucleus depends on the nuclear lamina, which is tightly associated with the inner nuclear membrane and on the interaction with the cytoskeleton. However, the mechanism connecting the differentiation state of a cell to the shape changes of its nucleus are not well understood. We investigated this question in early Drosophila embryos, where the nuclear shape changes from spherical to ellipsoidal together with a 2.5-fold increase in nuclear length during cellularization.
  
  
  RESULTS
  We identified two genes, kugelkern and kurzkern, required for nuclear elongation. In kugelkern- and kurzkern-depleted embryos, the nuclei reach only half the length of the wild-type nuclei at the end of cellularization. The reduced nuclear size affects chromocenter formation as marked by Heterochromatin protein 1 and expression of a specific set of genes, including early zygotic genes. kugelkern contains a putative coiled-coil domain in the N-terminal half of the protein, a nuclear localization signal (NLS), and a C-terminal CxxM-motif. The carboxyterminal CxxM motif is required for the targeting of Kugelkern to the inner nuclear membrane, where it colocalizes with lamins. Depending on the farnesylation motif, expression of kugelkern in Drosophila embryos or Xenopus cells induces overproliferation of nuclear membrane.
  
  
  CONCLUSIONS
  Kugelkern is so far the first nuclear protein, except for lamins, that contains a farnesylation site. Our findings suggest that Kugelkern is a rate-determining factor for nuclear size increase. We propose that association of farnesylated Kugelkern with the inner nuclear membrane induces expansion of nuclear surface area, allowing nuclear growth.
authors.affiliation: Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. a.haase@zmbh.uni-heidelberg.de
authors.forename: Annely
authors.initials: A
authors.lastname: Brandt
authors.forename: Fani
authors.initials: F
authors.lastname: Papagiannouli
authors.forename: Nicole
authors.initials: N
authors.lastname: Wagner
authors.forename: Michaela
authors.initials: M
authors.lastname: Wilsch-Bräuninger
authors.forename: Martina
authors.initials: M
authors.lastname: Braun
authors.forename: Eileen E
authors.initials: EE
authors.lastname: Furlong
authors.forename: Silke
authors.initials: S
authors.lastname: Loserth
authors.forename: Christian
authors.initials: C
authors.lastname: Wenzl
authors.forename: Fanny
authors.initials: F
authors.lastname: Pilot
authors.forename: Nina
authors.initials: N
authors.lastname: Vogt
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecuit
authors.forename: Georg
authors.initials: G
authors.lastname: Krohne
authors.forename: Jörg
authors.initials: J
authors.lastname: Grosshans
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D002467:Cell Nucleus / Q000648:ultrastructure*; D004330:Drosophila / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation; D007700:Kinetics; D007814:Larva / Q000378:metabolism / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000378:metabolism / Q000502:physiology / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D010641:Phenotype; D012313:RNA / Q000378:metabolism; D014981:Xenopus
chemical_list: D029721:Drosophila Proteins; D009687:Nuclear Proteins; C511714:kuk protein, Drosophila; C511715:kur protein, Drosophila; D012313:RNA