Accurate compartmentation/positioning of macromolecules and organelles is essential in eukaryotic cells. This proposal is concerned with a non-membranous barrier that subdivides the cytoplasm of yeast zygotes into regions of distinct parental origin. Examples of fibrous """"""""zones- of-exclusion"""""""" have previously been described in the cytoplasm of animal cells, some of which include intermediate filaments or actin. None is nearly as amenable to analysis as the zygote midzone complex (ZMC) that we have detected and will investigate in S. cerevisiae. The ZMC includes septins and is reminiscent of septin-containing structures at the bud neck that lie between the mother and daughter during the mitotic cell cycle. A Checkpoint for Redistribution of Mitochondria: Preliminary data lead to the hypothesis that the ZMC delays fusion of parental mitochondria and therefore ensures uniparental inheritance of the mitochondrial genome, as has been observed. To evaluate this hypothesis, we will 1) Learn whether septins in the ZMC have the dynamic properties that are required, and 2) Determine whether uniparental inheritance of the mitochondrial genome is compromised in septin mutants. A Checkpoint for Redistribution of Polysomes: To determine whether the ZMC is responsible for the delay in redistribution of polysomes, we will inquire whether the timing of their redistribution reflects 1) Their size, 2) Functionality of septins, or 3) Contact between nuclei (and spindle pole bodies), as is suggested by our Preliminary Data. Generality of Function: To further understand the scope of importance of the ZMC we will learn whether it governs the redistribution of novel particles in the cytoplasm, limits flux of membrane proteins of the cell cortex and nuclear envelope, and is responsible for the observation that parental vacuoles do not exchange components with each other in early zygotes. Given the apparent similarity to the bud neck as well as preliminary observations, we will determine whether the ZMC delimits a cortical zone within which exocytosis occurs. We will also learn whether septins of the ZMC undergo characteristic covalent modifications and whether these modifications are essential for the organization and functions of the ZMC. The final part of the proposal concerns identification of the target of a drug, forchlorfenuron that reversibly alters the structures of septin assemblages and interrupts redistribution of mitochondria in zygotes. Since this drug also perturbs animal cell septins, identification of its target will open unanticipated avenues of investigation related to septin biology.

Public Health Relevance

The partition which we will investigate provides a prototype of barriers that subcompartmentalize regions of the cytoplasm of eukaryotic cells. Our studies will help understand these very general principles, help elucidate functions of septins which are implicated in several diseases, clarify issues which are central to developmental cell biology and inheritance of the mitochondrial genome, and initiate the investigation of novel checkpoints that govern the distributions of organelles.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Membrane Biology and Protein Processing (MBPP)
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Ainsztein, Alexandra M
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Case Western Reserve University
Schools of Medicine
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Tartakoff, Alan Michael; Dulce, David; Landis, Elizabeth (2018) Delayed Encounter of Parental Genomes Can Lead to Aneuploidy in Saccharomyces cerevisiae. Genetics 208:139-151
Tartakoff, Alan M (2015) Cell biology of yeast zygotes, from genesis to budding. Biochim Biophys Acta 1853:1702-14
Zapanta Rinonos, Serendipity; Rai, Urvashi; Vereb, Sydney et al. (2014) Sequential logic of polarity determination during the haploid-to-diploid transition in Saccharomyces cerevisiae. Eukaryot Cell 13:1393-402
Tartakoff, Alan M; Wu, Di (2014) The axis of progression of disease. Cancer Inform 13:7-13
Ye, Wenduo; Lin, Wenbo; Tartakoff, Alan M et al. (2013) Nuclear import of aristaless-related homeobox protein via its NLS1 regulates its transcriptional function. Mol Cell Biochem 381:221-31
Tartakoff, Alan Michael; Aylyarov, Ilya; Jaiswal, Purnima (2013) Septin-containing barriers control the differential inheritance of cytoplasmic elements. Cell Rep 3:223-36
Zapanta Rinonos, Serendipity; Saks, Jeremy; Toska, Jonida et al. (2012) Flow cytometry-based purification of S. cerevisiae zygotes. J Vis Exp :e4197
Ye, Wenduo; Lin, Wenbo; Tartakoff, Alan M et al. (2011) Karyopherins in nuclear transport of homeodomain proteins during development. Biochim Biophys Acta 1813:1654-62
Tartakoff, Alan Michael; Jaiswal, Purnima (2009) Nuclear fusion and genome encounter during yeast zygote formation. Mol Biol Cell 20:2932-42