The proper positioning of the cell division plane is critical for cellular proliferation, and influences developmental processes such as cell differentiation, establishment of tissue architecture, and cell morphogenesis. The basic understanding of mechanisms of cytokinesis has broad relevance to human disease in areas such as cancer biology and stem cell biology. The general goal of this grant is to determine basic, fundamental mechanisms of cytokinesis and cell polarization. For our studies, we use a simple, genetically tractable model organism, the fission yeast Schizosaccharomyces pombe. A key process in division site placement is the localization of a cytokinesis factor mid1p to a medial cortical region overlying the nucleus. During mitosis, mid1p recruits other cytokinesis factors to this site to initiate the assembly of the actin-based contractile ring. We have discovered that diverse cellular components contribute to the localization of mid1p to this cortical location.
Our specific aims focus on characterizing new components that regulate this process: the endoplasmic reticulum, and a gradient of the pom1p kinase, which is indirectly set up by microtubules. Our innovative approaches include measuring the dynamic behavior of proteins inside of living cells and altering cell shapes using micro-fabricated chambers. These studies promise to provide a significant advance in the quantitative understanding of this conserved, universal process and elucidate general concepts of global spatial regulation used in building the cell.

Public Health Relevance

The placement of the cell division plane is a fundamental cellular process critical for cellular proliferation and development. Mistakes in cytokinesis are likely to contribute to the development of the cancer cell. These studies on elucidating basic mechanisms using fission yeast as a model organism are highly relevant towards understanding human cell biology and disease.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
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Deatherage, James F
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Columbia University (N.Y.)
Schools of Medicine
New York
United States
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Basu, Roshni; Munteanu, Emilia Laura; Chang, Fred (2014) Role of turgor pressure in endocytosis in fission yeast. Mol Biol Cell 25:679-87
Chang, Fred; Minc, Nicolas (2014) Electrochemical control of cell and tissue polarity. Annu Rev Cell Dev Biol 30:317-36
Saunders, Timothy E; Pan, Kally Z; Angel, Andrew et al. (2012) Noise reduction in the intracellular pom1p gradient by a dynamic clustering mechanism. Dev Cell 22:558-72
Basu, Roshni; Chang, Fred (2011) Characterization of dip1p reveals a switch in Arp2/3-dependent actin assembly for fission yeast endocytosis. Curr Biol 21:905-16
Minc, Nicolas; Burgess, David; Chang, Fred (2011) Influence of cell geometry on division-plane positioning. Cell 144:414-26
Minc, Nicolas; Chang, Fred (2010) Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe. Curr Biol 20:710-6
Yonetani, Ann; Chang, Fred (2010) Regulation of cytokinesis by the formin cdc12p. Curr Biol 20:561-6
Bathe, Mark; Chang, Fred (2010) Cytokinesis and the contractile ring in fission yeast: towards a systems-level understanding. Trends Microbiol 18:38-45
Chang, Fred; Martin, Sophie G (2009) Shaping fission yeast with microtubules. Cold Spring Harb Perspect Biol 1:a001347
Minc, Nicolas; Bratman, Scott V; Basu, Roshni et al. (2009) Establishing new sites of polarization by microtubules. Curr Biol 19:83-94

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