TY - JOUR
T1 - MAN1 and emerin have overlapping function(s) essential for chromosome segregation and cell division in Caenorhabditis elegans
AU - Liu, Jun
AU - Lee, Kenneth K.
AU - Segura-Totten, Miriam
AU - Neufeld, Ester
AU - Wilson, Katherine L.
AU - Gruenbaum, Yosef
PY - 2003/4/15
Y1 - 2003/4/15
N2 - Emerin and MAN1 are LEM domain-containing integral membrane proteins of the vertebrate nuclear envelope. The function of MAN1 is unknown, whereas emerin is known to interact with nuclear lamins, barrier-to-autointegration factor (BAF), nesprin-1α, and a transcription repressor. Mutations in emerin cause X-linked reces-sive Emery-Dreifuss muscular dystrophy. Emerin and MAN1 homologs are both conserved in Caenorhabditis elegans, but loss of Ce-emerin has no detectable phenotype. We therefore used C. elegans to test the hypothesis that Ce-MAN1 overlaps functionally with Ce-emerin. Supporting this model, Ce-MAN1 interacted directly with Ce-lamin and Ce-BAF in vitro and required Ce-lamin for its nuclear envelope localization. Interestingly, RNA interference-mediated removal of ∼-90% of Ce-MAN1 was lethal to ∼-15% of embryos. However, in the absence of Ce-emerin, ∼-90% reduction of Ce-MAN1 was lethal to all embryos by the 100-cell stage, with a phenotype involving repeated cycles of anaphase chromosome bridging and cytokinesis ["cell untimely torn" (cut) phenotype]. Immunostaining showed that the anaphase-bridged chromatin specifically retained a mitosis-specific phosphohistone H3 epitope and failed to recruit detectable Ce-lamin or Ce-BAF. These findings show that LEM domain proteins are essential for 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.
AB - Emerin and MAN1 are LEM domain-containing integral membrane proteins of the vertebrate nuclear envelope. The function of MAN1 is unknown, whereas emerin is known to interact with nuclear lamins, barrier-to-autointegration factor (BAF), nesprin-1α, and a transcription repressor. Mutations in emerin cause X-linked reces-sive Emery-Dreifuss muscular dystrophy. Emerin and MAN1 homologs are both conserved in Caenorhabditis elegans, but loss of Ce-emerin has no detectable phenotype. We therefore used C. elegans to test the hypothesis that Ce-MAN1 overlaps functionally with Ce-emerin. Supporting this model, Ce-MAN1 interacted directly with Ce-lamin and Ce-BAF in vitro and required Ce-lamin for its nuclear envelope localization. Interestingly, RNA interference-mediated removal of ∼-90% of Ce-MAN1 was lethal to ∼-15% of embryos. However, in the absence of Ce-emerin, ∼-90% reduction of Ce-MAN1 was lethal to all embryos by the 100-cell stage, with a phenotype involving repeated cycles of anaphase chromosome bridging and cytokinesis ["cell untimely torn" (cut) phenotype]. Immunostaining showed that the anaphase-bridged chromatin specifically retained a mitosis-specific phosphohistone H3 epitope and failed to recruit detectable Ce-lamin or Ce-BAF. These findings show that LEM domain proteins are essential for 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.
UR - http://www.scopus.com/inward/record.url?scp=0037446880&partnerID=8YFLogxK
U2 - 10.1073/pnas.0730821100
DO - 10.1073/pnas.0730821100
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C2 - 12684533
AN - SCOPUS:0037446880
SN - 0027-8424
VL - 100
SP - 4598
EP - 4603
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 8
ER -