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Molecular and Cellular Biology, December 2002, p. 8491-8505, Vol. 22, No. 24
0270-7306/02/$04.00+0     DOI: 10.1128/MCB.22.24.8491-8505.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

The Ran GTPase System in Fission Yeast Affects Microtubules and Cytokinesis in Cells That Are Competent for Nucleocytoplasmic Protein Transport

Sandra S. Salus,1,2 Janos Demeter,2,{dagger} and Shelley Sazer1,2*

Interdepartmental Program in Cell and Molecular Biology,1 Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 770302

Received 1 July 2002/ Returned for modification 20 August 2002/ Accepted 18 September 2002

Misregulation of the evolutionarily conserved GTPase Ran in fission yeast results in defects in several cellular processes in cells that are competent for nucleocytoplasmic protein transport. These results suggest that transport is neither the only nor the primary Ran-dependent process in living cells. The ability of Ran to independently regulate multiple cellular processes in vivo is demonstrated by showing that (i) eight different transport-competent RanGEF (guanine nucleotide exchange factor) mutants have defects in mitotic spindle formation; (ii) the RanGEF temperature-sensitive mutant pim1-d1 has abnormal actin ring structures at the septum. Overexpression of Imp2p, which specifically destabilizes these structures, restores viability. (iii) Ran-dependent processes differ in their requirements for active Ran in vivo. Microtubule function, cytokinesis, and nuclear envelope structure are the Ran-dependent processes most sensitive to the amount of Ran protein in the cell, whereas nucleocytoplasmic protein transport is the most robust. Therefore, the ability of Ran from Schizosaccharomyces pombe to independently regulate multiple cellular processes may reflect differences in its interactions with the binding proteins that mediate these functions and explain the complex phenotypic consequences of its misregulation in vivo.


* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Phone: (713) 798-4531. Fax: (713) 796-9438. E-mail: ssazer{at}bcm.tmc.edu.

{dagger} Present address: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305.


Molecular and Cellular Biology, December 2002, p. 8491-8505, Vol. 22, No. 24
0022-538X/02/$04.00+0     DOI: 10.1128/MCB.22.24.8491-8505.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.




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