The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis

Christopher J. Bakal, Dina Finan, José Larose, Clark Wells, Gerald Gish, Sarang Kulkarni, Paulo Desepulveda, Andrew Wilde, Robert Rottapel

Research output: Contribution to journalArticle

40 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9529-9534
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume102
Issue number27
DOIs
StatePublished - Jul 5 2005
Externally publishedYes

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rho GTP-Binding Proteins
Prometaphase
Guanosine Triphosphate
Mitosis
Prophase
Microtubules
Spindle Apparatus
Interphase
Actins

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis. / Bakal, Christopher J.; Finan, Dina; Larose, José; Wells, Clark; Gish, Gerald; Kulkarni, Sarang; Desepulveda, Paulo; Wilde, Andrew; Rottapel, Robert.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 102, No. 27, 05.07.2005, p. 9529-9534.

Research output: Contribution to journalArticle

Bakal, CJ, Finan, D, Larose, J, Wells, C, Gish, G, Kulkarni, S, Desepulveda, P, Wilde, A & Rottapel, R 2005, 'The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis', Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 27, pp. 9529-9534. https://doi.org/10.1073/pnas.0504190102
Bakal, Christopher J. ; Finan, Dina ; Larose, José ; Wells, Clark ; Gish, Gerald ; Kulkarni, Sarang ; Desepulveda, Paulo ; Wilde, Andrew ; Rottapel, Robert. / The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis. In: Proceedings of the National Academy of Sciences of the United States of America. 2005 ; Vol. 102, No. 27. pp. 9529-9534.
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AU - Larose, José

AU - Wells, Clark

AU - Gish, Gerald

AU - Kulkarni, Sarang

AU - Desepulveda, Paulo

AU - Wilde, Andrew

AU - Rottapel, Robert

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N2 - 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.

AB - 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.

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