The development of cell shape and three-dimensional organizational (cellular morphogenesis) is a process of fundamental importance in cellular and developmental biology. Defects in cellular morphogenesis are also implicated in disease states such as birth defects and cancer. The long-term of the research proposed here is to exploit the remarkable experimental advantages of the unicellular eukaryote Saccharomyces cerevisiae (yeast) to elucidate general principles and mechanisms of cellular morphogenesis. A feature of cellular morphogenesis in most cells is the development of cell polarity along an appropriate axis, and loss of normal polarity is an early event in the development of epithelial tumors. As yeast chooses non-random sites for budding and polarizes its cytoskeleton and cell- surface growth along the axis defined by the bid site, it provides an attractive model system for investigation of cell polarization. The specific studies proposed here will use a combination of genetic, molecular biological, biochemical, and cell biological methods to investigate two sets of problems. (I) How do persistent spatial markers in the cell cortex and a GTPase signaling module (based on the Ras-like Rsr1p) determine the bipolar pattern of bud-site selection (as normally seen in diploid cells)? (II) How does a second GTPase signaling module (based on the Rho-like Cdc42p) control the establishment of cytoskeletal polarization toward the selected bud site? Cytoplasmic division (cytokinesis) is another important aspect of cellular morphogenesis as well as the cellular reproduction cycle; defects in cytokinesis also appear to contribute to the development of various kinds of cancer. The septins are a novel family of proteins first discovered on the basis of their involvement in cytokinesis in yeast. They are now known to be involved in cytokinesis in insect and mammalian cells as well, and the available evidence suggests that they also have a variety of other roles in the organization of the cell surface. The studies proposed here will use a combination of genetic molecular biological, biochemical, and cell biological methods to investigate a third set of problems: (III) How do the septins assemble and associate with the plasma membrane? What other proteins do they organize at the cell cortex? What are the roles of the septins both in ordinary cytokinesis and in the specialized process by which spores are formed?

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37GM031006-19
Application #
6476431
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Deatherage, James F
Project Start
1982-07-01
Project End
2004-11-30
Budget Start
2001-12-01
Budget End
2002-11-30
Support Year
19
Fiscal Year
2002
Total Cost
$392,576
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Genetics
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Onishi, Masayuki; Pringle, John R (2016) Analysis of Rho-GTPase Activity During Budding Yeast Cytokinesis. Methods Mol Biol 1369:205-18
Lee, I-Ju; Wang, Ning; Hu, Wen et al. (2014) Regulation of spindle pole body assembly and cytokinesis by the centrin-binding protein Sfi1 in fission yeast. Mol Biol Cell 25:2735-49
Onishi, Masayuki; Ko, Nolan; Nishihama, Ryuichi et al. (2013) Distinct roles of Rho1, Cdc42, and Cyk3 in septum formation and abscission during yeast cytokinesis. J Cell Biol 202:311-29
Tuo, Shanshan; Nakashima, Kenichi; Pringle, John R (2013) Role of endocytosis in localization and maintenance of the spatial markers for bud-site selection in yeast. PLoS One 8:e72123
Tuo, Shanshan; Nakashima, Kenichi; Pringle, John R (2012) Apparent defect in yeast bud-site selection due to a specific failure to splice the pre-mRNA of a regulator of cell-type-specific transcription. PLoS One 7:e47621
Pollard, Luther W; Onishi, Masayuki; Pringle, John R et al. (2012) Fission yeast Cyk3p is a transglutaminase-like protein that participates in cytokinesis and cell morphogenesis. Mol Biol Cell 23:2433-44
Wloka, Carsten; Nishihama, Ryuichi; Onishi, Masayuki et al. (2011) Evidence that a septin diffusion barrier is dispensable for cytokinesis in budding yeast. Biol Chem 392:813-29
Nishihama, Ryuichi; Onishi, Masayuki; Pringle, John R (2011) New insights into the phylogenetic distribution and evolutionary origins of the septins. Biol Chem 392:681-7
Wu, Jian-Qiu; Ye, Yanfang; Wang, Ning et al. (2010) Cooperation between the septins and the actomyosin ring and role of a cell-integrity pathway during cell division in fission yeast. Genetics 186:897-915
Fang, Xiaodong; Luo, Jianying; Nishihama, Ryuichi et al. (2010) Biphasic targeting and cleavage furrow ingression directed by the tail of a myosin II. J Cell Biol 191:1333-50

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