Developmental control of nuclear size and shape by Kugelkern and Kurzkern.
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.
Brandt
Annely
A
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH), Im Neuenheimer Feld 282, 69120 Heidelberg, Germany. a.haase@zmbh.uni-heidelberg.de
Papagiannouli
Fani
F
Wagner
Nicole
N
Wilsch-Bräuninger
Michaela
M
Braun
Martina
M
Furlong
Eileen E
EE
Loserth
Silke
S
Wenzl
Christian
C
Pilot
Fanny
F
Vogt
Nina
N
Lecuit
Thomas
T
Krohne
Georg
G
Grosshans
Jörg
J
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
D029721:Drosophila Proteins; D009687:Nuclear Proteins; C511714:kuk protein, Drosophila; C511715:kur protein, Drosophila; D012313:RNA