MEL-28 is downstream of the Ran cycle and is required for nuclear-envelope function and chromatin maintenance.
Early embryonic development depends on the faithful execution of basic cell biological processes whose coordination remains largely unknown. With a global network analysis, we found MEL-28 to be associated with two types of complexes, one implicated in nuclear-envelope function and the other in chromatin organization. Here, we show that MEL-28, a protein that shuttles between the nucleus and the kinetochore during the cell cycle, is required for the structural and functional integrity of the nuclear envelope. In addition, mel-28(RNAi) embryos exhibit defects in chromosome condensation, pronuclear migration, kinetochore assembly, and spindle assembly. This combination of mel-28(RNAi) phenotypes resemble those caused by depleting members of the Ran cycle in C. elegans, a conserved cellular signaling pathway that is required for mitotic spindle assembly, nuclear-envelope reformation after mitosis, and nucleocytoplasmic exchange (reviewed in). Although MEL-28 localization to the nuclear periphery is not dependent on nuclear pore components, it is dependent on RAN-1 and other key components of the Ran cycle. Thus, MEL-28 is downstream of the Ran cycle and is required for both proper nuclear-envelope function and chromatin maintenance.
Fernandez
Anita G
AG
Center for Comparative Functional Genomics, Department of Biology, New York University, New York, New York 10003, USA.
Piano
Fabio
F
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology*; D002453:Cell Cycle / Q000502:physiology; D018385:Centrosome / Q000502:physiology; D002843:Chromatin / Q000378:metabolism* / Q000648:ultrastructure; D004268:DNA-Binding Proteins; D018386:Kinetochores / Q000378:metabolism; D009685:Nuclear Envelope / Q000502:physiology* / Q000648:ultrastructure; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism; D020931:ran GTP-Binding Protein / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C514979:mel-28 protein, C elegans; D020931:ran GTP-Binding Protein