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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Wells, Clark D. Gish, Gerald Kulkarni, Sarang Bakal, Christopher J. Rottapel, Robert Finan, Dina Larose, José Wilde, Andrew Desepulveda, Paulo |
| Description | Author Affiliation: Bakal CJ ( Department of Medical Biophysics, University of Toronto, 1 King's College Circle, Toronto, ON, Canada M5S 1A8.); |
| Abstract | Rho GTPases regulate reorganization of actin and microtubule cytoskeletal structures during both interphase and mitosis. The timing and subcellular compartment in which Rho GTPases are activated is controlled by the large family of Rho GTP exchange factors (RhoGEFs). Here, we show that the microtubule-associated RhoGEF Lfc is required for the formation of the mitotic spindle during prophase/prometaphase. The inability of cells to assemble a functioning spindle after Lfc inhibition resulted in a delay in mitosis and an accumulation of prometaphase cells. Inhibition of Lfc's primary target Rho GTPase during prophase/prometaphase, or expression of a catalytically inactive mutant of Lfc, also prevented normal spindle assembly and resulted in delays in mitotic progression. Coinjection of constitutively active Rho GTPase rescued the spindle defects caused by Lfc inhibition, suggesting the requirement of RhoGTP in regulating spindle assembly. Lastly, we implicate mDia1 as an important effector of Lfc signaling. These findings demonstrate a role for Lfc, Rho, and mDia1 during mitosis. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 27 |
| Volume Number | 102 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2005-07-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Guanine Nucleotide Exchange Factors Metabolism Prophase Physiology Proto-Oncogene Proteins Spindle Apparatus Animals Cell Line DNA Primers GTP-Binding Proteins Genetics Genetic Vectors Mice Microinjections Microscopy, Fluorescence Rho Guanine Nucleotide Exchange Factors Rho GTP-Binding Proteins Comparative Study Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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