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Spatial regulation of Cdc42 by its GTPase-activating proteins Rga1 and Bem2 in budding yeast Saccharomyces cerevisiae.

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Format:
Book
Thesis/Dissertation
Author/Creator:
Tong, Zongtian.
Contributor:
Bi, Erfei, advisor.
University of Pennsylvania.
Language:
English
Subjects (All):
Cytology.
Genetics.
Molecular biology.
0307.
0369.
0379.
Penn dissertations--Biology.
Biology--Penn dissertations.
Local Subjects:
Penn dissertations--Biology.
Biology--Penn dissertations.
0307.
0369.
0379.
Physical Description:
125 pages
Contained In:
Dissertation Abstracts International 70-02B.
System Details:
Mode of access: World Wide Web.
text file
Summary:
Cdc42 is an evolutionarily conserved Rho-like GTPase that is essential to establishing cell polarity in eukaryotes ranging from yeast to humans. In order to precisely control cell polarization, Cdc42 activation must be restricted spatially and temporally. Here, using the budding yeast Saccharomyces cerevisiae as a model system, I characterized the spatial regulation of Cdc42 by its GTPase-activating proteins (GAPs) by a combination of genetic, biochemical, and cell biological approaches. The cycling of Cdc42 between its GTP- and GDP-bound states is regulated by its guanine nucleotide exchange factor (GEF), Cdc24, and its GAPs, Rga1, Rga2, Bem3, and Bem2. First, I showed that the Cdc42 GAP, Rga1, establishes an exclusion zone at the division site that blocks subsequent polarization within that site. In the absence of localized Rga1 GAP activity, new buds do in fact form within the old division site. Thus, Cdc42 activators and GAPs establish concentric zones of action such that polarization is directed to occur adjacent to but not within the previous division site. Next, I found that Rga1 and Bem2 during S/G2/M phases. The loss of Rga1 and Bem2 causes a loss-of-polarity phenotype, leading to lethality or temperature sensitive growth defect of the cells. Finally, the bud neck localization and GAP activity of Bem2 appear to be required for its role in gatekeeper function. Overall, the various GAPs of Cdc42 spatially and temporally regulate its activity, which is essential to its role in controlling polarized organization of actin cytoskeleton and septins.
Notes:
Thesis (Ph.D. in Biology) -- University of Pennsylvania, 2008.
Source: Dissertation Abstracts International, Volume: 70-02, Section: B, page: 0847.
Adviser: Erfei Bi.
Local Notes:
School code: 0175.
ISBN:
9781109008807
Access Restriction:
Restricted for use by site license.

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