The endomembrane system of all eukaryotic cells consists of a collection of membrane bound compartments. Movement of materials amongst these compartments is achieved by the regulated trafficking of cargo vesicles between compartments. In the process of differentiation, higher cells re-organize their internal membranes in an enormous variety of ways; expanding or specializing certain compartments, distributing them differently in the cell, or carrying vesicles to new destinations. Though these rearrangements are often critical to the function of the differentiated cell, little is known about how these specializations are imposed on the basic pattern of the secretory pathway. Spore formation in yeast involves a cell division that requires a similar organized rearrangement of the secretory apparatus. In this instance, retargetting of secretory vesicles gives rise to a new membrane compartment, the prospore membrane. This membrane arises by the redirection of secretory vesicles away from the plasma membrane to the cell interior. Prospore membrane formation therefore serves as a model for understanding the developmentally programmed reorganization of cellular membranes. In addition to the retargetting of secretory vesicles, new genetic requirements are imposed on the fusion and trafficking of these vesicles during sporulation. SPO2O encodes a SNARE protein essential for secretory vesicle fusion in sporulating cells. In order to understand the basis for this requirement, mutations in SPO2O that interfere specifically with its ability to support vesicle fusion in sporulating cells will be isolated. These mutations will be used to isolate genetic suppressors of the SPO2O defect. The rearrangement of the secretory pathway during sporulation is coordinated with the meiotic divisions. How this coordination is established will be investigated by examining the affect of mutations in cell-cycle regulatory genes on secretory vesicle redirection as well as examining the role in sporulation of two cell cycle regulated kinases that bind directly to Spo2Op. Finally, prospore membrane formation cannot initiate without the appearance of a sporulation-specific modification on the cytoplasmic face of the spindle pole body (SPB). SPO21 encodes a protein required for prospore membrane formation and may be necessary for this modification. The model that Spo2lp is a sporulation-specific component of the SPB will be tested and the role of Spo2 Ip in SPB modification examined.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM062184-01
Application #
6225813
Study Section
Cell Development and Function Integrated Review Group (CDF)
Program Officer
Shapiro, Bert I
Project Start
2001-01-01
Project End
2005-12-31
Budget Start
2001-01-01
Budget End
2001-12-31
Support Year
1
Fiscal Year
2001
Total Cost
$267,240
Indirect Cost
Name
State University New York Stony Brook
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Ucisik-Akkaya, Esma; Leatherwood, Janet K; Neiman, Aaron M (2014) A genome-wide screen for sporulation-defective mutants in Schizosaccharomyces pombe. G3 (Bethesda) 4:1173-82
Mathieson, Erin M; Suda, Yasuyuki; Nickas, Mark et al. (2010) Vesicle docking to the spindle pole body is necessary to recruit the exocyst during membrane formation in Saccharomyces cerevisiae. Mol Biol Cell 21:3693-707
Mathieson, Erin M; Schwartz, Cindi; Neiman, Aaron M (2010) Membrane assembly modulates the stability of the meiotic spindle-pole body. J Cell Sci 123:2481-90
Lisa-Santamaría, Patricia; Neiman, Aaron M; Cuesta-Marbán, Alvaro et al. (2009) Human initiator caspases trigger apoptotic and autophagic phenotypes in Saccharomyces cerevisiae. Biochim Biophys Acta 1793:561-71
Yang, Hui-Ju; Nakanishi, Hideki; Liu, Song et al. (2008) Binding interactions control SNARE specificity in vivo. J Cell Biol 183:1089-100
Yan, Hongyan; Ge, Wanzhong; Chew, Ting Gang et al. (2008) The meiosis-specific Sid2p-related protein Slk1p regulates forespore membrane assembly in fission yeast. Mol Biol Cell 19:3676-90
Pablo-Hernando, M Evangelina; Arnaiz-Pita, Yolanda; Nakanishi, Hideki et al. (2007) Cdc15 is required for spore morphogenesis independently of Cdc14 in Saccharomyces cerevisiae. Genetics 177:281-93
Liu, Song; Wilson, Kirilee A; Rice-Stitt, Travis et al. (2007) In vitro fusion catalyzed by the sporulation-specific t-SNARE light-chain Spo20p is stimulated by phosphatidic acid. Traffic 8:1630-43
Nakanishi, Hideki; Suda, Yasuyuki; Neiman, Aaron M (2007) Erv14 family cargo receptors are necessary for ER exit during sporulation in Saccharomyces cerevisiae. J Cell Sci 120:908-16
Nakanishi, Hideki; Morishita, Masayo; Schwartz, Cindi L et al. (2006) Phospholipase D and the SNARE Sso1p are necessary for vesicle fusion during sporulation in yeast. J Cell Sci 119:1406-15

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