S. cerevisiae is an excellent organism for studies of cell polarity development due to its powerful genetics, its simplicity, the ability to observe polarity development synchronously in a cell population, and existence of numerous mutations and molecular markers for cell polarity. Studies will determine how Cdc42 GTPase controls actin organization, and how actin mediates polarized endocytosis. Thirty-seven site-directed cdc42 mutants will be characterized biochemically in permeabilized yeast and in actin-assembly competent yeast extracts to relate biochemical activities to in vivo functions, and used in genetic screens to identify components of downstream pathways. Roles for Cdc42 effector Pak kinases in morphogenesis will be elucidated by genetic and chemical-genetic strategies. Special cdc42 alleles defective in pseudohyphal growth will be studied to provide a deeper understanding of the molecular basis for fungal dimorphism, a characteristic of many fungal pathogens. Finally, how a complex set of interacting proteins links endocytic membranes to the Arp2/3 complex, and how these proteins are regulated by novel Ark kinases discovered in this laboratory, will be investigated.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM050399-07
Application #
6627189
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Deatherage, James F
Project Start
1997-01-01
Project End
2004-12-31
Budget Start
2003-01-01
Budget End
2003-12-31
Support Year
7
Fiscal Year
2003
Total Cost
$335,180
Indirect Cost
Name
University of California Berkeley
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
124726725
City
Berkeley
State
CA
Country
United States
Zip Code
94704
Lu, Rebecca; Drubin, David G; Sun, Yidi (2016) Clathrin-mediated endocytosis in budding yeast at a glance. J Cell Sci 129:1531-6
Sun, Yidi; Leong, Nicole T; Wong, Tiffany et al. (2015) A Pan1/End3/Sla1 complex links Arp2/3-mediated actin assembly to sites of clathrin-mediated endocytosis. Mol Biol Cell 26:3841-56
Murphy, Mark W; Lee, John K; Rojo, Sandra et al. (2015) An ancient protein-DNA interaction underlying metazoan sex determination. Nat Struct Mol Biol 22:442-51
Lewellyn, Eric B; Pedersen, Ross T A; Hong, Jessica et al. (2015) An Engineered Minimal WASP-Myosin Fusion Protein Reveals Essential Functions for Endocytosis. Dev Cell 35:281-94
Cortesio, Christa L; Lewellyn, Eric B; Drubin, David G (2015) Control of lipid organization and actin assembly during clathrin-mediated endocytosis by the cytoplasmic tail of the rhomboid protein Rbd2. Mol Biol Cell 26:1509-22
Peng, Yutian; Grassart, Alexandre; Lu, Rebecca et al. (2015) Casein kinase 1 promotes initiation of clathrin-mediated endocytosis. Dev Cell 32:231-40
Weinberg, Jasper S; Drubin, David G (2014) Regulation of clathrin-mediated endocytosis by dynamic ubiquitination and deubiquitination. Curr Biol 24:951-9
Buser, Christopher; Drubin, David G (2013) Ultrastructural imaging of endocytic sites in Saccharomyces cerevisiae by transmission electron microscopy and immunolabeling. Microsc Microanal 19:381-92
Zhao, Hongxia; Michelot, Alphee; Koskela, Essi V et al. (2013) Membrane-sculpting BAR domains generate stable lipid microdomains. Cell Rep 4:1213-23
Sun, Yidi; Drubin, David G (2012) The functions of anionic phospholipids during clathrin-mediated endocytosis site initiation and vesicle formation. J Cell Sci 125:6157-65

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