A lamin-dependent pathway that regulates nuclear organization, cell cycle progression and germ cell development

Ayelet Margalit, Jun Liu, Alexandra Fridkin, Katherine Lee Wilson, Yosef Gruenbaum

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

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 ∼15% embryonic lethality. However in worms that lack Ce-emerin, a ∼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.

Original languageEnglish (US)
Title of host publicationNovartis Foundation Symposium
Pages231-240
Number of pages10
Volume264
Publication statusPublished - 2005

Publication series

NameNovartis Foundation Symposium
Volume264
ISSN (Print)15282511

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Margalit, A., Liu, J., Fridkin, A., Wilson, K. L., & Gruenbaum, Y. (2005). A lamin-dependent pathway that regulates nuclear organization, cell cycle progression and germ cell development. In Novartis Foundation Symposium (Vol. 264, pp. 231-240). (Novartis Foundation Symposium; Vol. 264).