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Vol. 12, Issue 5, 1239-1255, May 2001
Department of Pharmacology and Cancer Biology, Duke University
Medical Center, Durham, North Carolina 27710
The highly conserved small GTPase Cdc42p is a key regulator of cell
polarity and cytoskeletal organization in eukaryotic cells. Multiple
effectors of Cdc42p have been identified, although it is unclear how
their activities are coordinated to produce particular cell behaviors.
One strategy used to address the contributions made by different
effector pathways downstream of small GTPases has been the use of
"effector-loop" mutants of the GTPase that selectively impair only
a subset of effector pathways. We now report the generation and
preliminary characterization of a set of effector-loop mutants of
Saccharomyces cerevisiae CDC42. These mutants define
genetically separable pathways influencing actin or septin
organization. We have characterized the phenotypic defects of these
mutants and the binding defects of the encoded proteins to known yeast
Cdc42p effectors in vitro. The results suggest that these effectors
cannot account for the observed phenotypes, and therefore that unknown
effectors exist that affect both actin and septin organization. The
availability of partial function alleles of CDC42 in a
genetically tractable system serves as a useful starting point for
genetic approaches to identify such novel effectors.
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