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The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2005 Jul 05; Vol. 102 (27), pp. 9529-34. Date of Electronic Publication: 2005 Jun 23. - Publication Year :
- 2005
-
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.
- Subjects :
- Animals
Cell Line
DNA Primers
GTP-Binding Proteins genetics
Genetic Vectors
Guanine Nucleotide Exchange Factors genetics
Humans
Mice
Microinjections
Microscopy, Fluorescence
Proto-Oncogene Proteins genetics
Rats
Rho Guanine Nucleotide Exchange Factors
rho GTP-Binding Proteins metabolism
Guanine Nucleotide Exchange Factors metabolism
Prophase physiology
Proto-Oncogene Proteins metabolism
Spindle Apparatus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 102
- Issue :
- 27
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 15976019
- Full Text :
- https://doi.org/10.1073/pnas.0504190102