Ect2 and MgcRacGAP Regulate the Activation and Function of Cdc42 in Mitosis

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2005 Jan 12

PMID 15642749

Citations 59

Authors

Fabian Oceguera-Yanez

Kazuhiro Kimura

Shingo Yasuda

Chiharu Higashida

Toshio Kitamura

Yasushi Hiraoka

Tokuko Haraguchi

Shuh Narumiya

Affiliations

Soon will be listed here.

Abstract

Although Rho regulates cytokinesis, little was known about the functions in mitosis of Cdc42 and Rac. We recently suggested that Cdc42 works in metaphase by regulating bi-orient attachment of spindle microtubules to kinetochores. We now confirm the role of Cdc42 by RNA interference and identify the mechanisms for activation and down-regulation of Cdc42. Using a pull-down assay, we found that the level of GTP-Cdc42 elevates in metaphase, whereas the level of GTP-Rac does not change significantly in mitosis. Overexpression of dominant-negative mutants of Ect2 and MgcRacGAP, a Rho GTPase guanine nucleotide exchange factor and GTPase activating protein, respectively, or depletion of Ect2 by RNA interference suppresses this change of GTP-Cdc42 in mitosis. Depletion of Ect2 also impairs microtubule attachment to kinetochores and causes prometaphase delay and abnormal chromosomal segregation, as does depletion of Cdc42 or expression of the Ect2 and MgcRacGAP mutants. These results suggest that Ect2 and MgcRacGAP regulate the activation and function of Cdc42 in mitosis.

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