A lamin-dependent pathway that regulates nuclear organization, cell cycle progression and germ cell development.
The C. elegans genome encodes a single lamin protein (Ce-lamin), three LEM domain proteins (Ce-emerin, Ce-MAN1 and LEM-3) and a single BAF protein (Ce-BAF). Down-regulation of Ce-lamin causes embryonic lethality. Abnormalities include rapid changes in nuclear morphology during interphase, inability of cells to complete mitosis, abnormal condensation of chromatin, clustering of nuclear pore complexes (NPCs), and missing or abnormal germ cells. Ce-emerin and Ce-MAN1 are both embedded in the inner nuclear membrane, and both bind Ce-lamin and Ce-BAF; in addition, both require Ce-lamin for their localization. Mutations in human emerin cause X-linked recessive Emery-Dreifuss muscular dystrophy. In C. elegans, loss of Ce-emerin alone has no detectable phenotype, while loss of 90% Ce-MAN1 causes approximately 15% embryonic lethality. However in worms that lack Ce-emerin, a approximately 90% reduction of Ce-MAN1 is lethal to all embryos by the 100-cell stage, with a phenotype involving chromatin condensation and repeated cycles of anaphase chromosome bridging and cytokinesis. The anaphase-bridged chromatin retained a mitosis-specific phosphohistone H3 epitope, and failed to recruit detectable Ce-lamin or Ce-BAF. Down-regulation of Ce-BAF showed similar phenotypes. These findings suggest that lamin, LEM-domain proteins and BAF are part of a lamina network essential for chromatin organization and cell division, and that Ce-emerin and Ce-MAN1 share at least one and possibly multiple overlapping functions, which may be relevant to Emery-Dreifuss muscular dystrophy.
Margalit
Ayelet
A
Department of Genetics, The Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
Liu
Jun
J
Fridkin
Alexandra
A
Wilson
Katherine L
KL
Gruenbaum
Yosef
Y
D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D005854:Germ Cells / Q000254:growth & development*; D006801:Humans; D034882:Lamins / Q000378:metabolism*; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000378:metabolism; D009685:Nuclear Envelope / Q000502:physiology*; D015530:Nuclear Matrix / Q000502:physiology; D009687:Nuclear Proteins / Q000378:metabolism*; D015398:Signal Transduction
D034882:Lamins; D009687:Nuclear Proteins