TY - JOUR
T1 - MEL-28 Is Downstream of the Ran Cycle and Is Required for Nuclear-Envelope Function and Chromatin Maintenance
AU - Fernandez, Anita G.
AU - Piano, Fabio
N1 - Funding Information:
The 12G10 anti-tubulin monoclonal antibody generated by J. Frankel and E.M. Nelsen was obtained from the Developmental Studies Hybridoma Bank developed under the auspices of the National Institute of Child Health and Human Development (NICHD) and maintained by The University of Iowa, Department of Biological Sciences. Nematode strains used in this work were provided by the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health (NIH) National Center for Research Resources (NCRR). We gratefully acknowledge Iain Cheeseman and Arshad Desai for antibodies and counsel; Tamer Hadi for excellent technical assistance; and Kris Gunsalus, Sabbi Lall, and Scott Weatherbee for critical reading of the manuscript. In addition, we gratefully acknowledge Kris Gunsalus for helpful discussions and advice throughout this project. A.G.F. is funded by grant DBI-0408803 from the National Science Foundation (NSF), and F.P. is funded by grant R01-HD046236 from the NIH.
PY - 2006/9/5
Y1 - 2006/9/5
N2 - 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 [1]. 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 [2], a conserved cellular signaling pathway that is required for mitotic spindle assembly, nuclear-envelope reformation after mitosis, and nucleocytoplasmic exchange (reviewed in [3-8]). 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.
AB - 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 [1]. 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 [2], a conserved cellular signaling pathway that is required for mitotic spindle assembly, nuclear-envelope reformation after mitosis, and nucleocytoplasmic exchange (reviewed in [3-8]). 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.
KW - CELLBIO
UR - http://www.scopus.com/inward/record.url?scp=33747821629&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33747821629&partnerID=8YFLogxK
U2 - 10.1016/j.cub.2006.07.071
DO - 10.1016/j.cub.2006.07.071
M3 - Article
C2 - 16950115
AN - SCOPUS:33747821629
SN - 0960-9822
VL - 16
SP - 1757
EP - 1763
JO - Current Biology
JF - Current Biology
IS - 17
ER -