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.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM056836-17
Application #
8617282
Study Section
Nuclear and Cytoplasmic Structure/Function and Dynamics Study Section (NCSD)
Program Officer
Deatherage, James F
Project Start
1998-02-01
Project End
2015-02-28
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
17
Fiscal Year
2014
Total Cost
$456,738
Indirect Cost
$170,560
Name
Columbia University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Atilgan, Erdinc; Magidson, Valentin; Khodjakov, Alexey et al. (2015) Morphogenesis of the Fission Yeast Cell through Cell Wall Expansion. Curr Biol 25:2150-7
Zhou, Zhou; Munteanu, Emilia Laura; He, Jun et al. (2015) The contractile ring coordinates curvature-dependent septum assembly during fission yeast cytokinesis. Mol Biol Cell 26:78-90
Chang, Fred; Huang, Kerwyn Casey (2014) How and why cells grow as rods. BMC Biol 12:54
Haupt, Armin; Campetelli, Alexis; Bonazzi, Daria et al. (2014) Electrochemical regulation of budding yeast polarity. PLoS Biol 12:e1002029
Pan, Kally Z; Saunders, Timothy E; Flor-Parra, Ignacio et al. (2014) Cortical regulation of cell size by a sizer cdr2p. Elife 3:e02040
Chang, Fred; Minc, Nicolas (2014) Electrochemical control of cell and tissue polarity. Annu Rev Cell Dev Biol 30:317-36
Basu, Roshni; Munteanu, Emilia Laura; Chang, Fred (2014) Role of turgor pressure in endocytosis in fission yeast. Mol Biol Cell 25:679-87
Atilgan, Erdinc; Burgess, David; Chang, Fred (2012) Localization of cytokinesis factors to the future cell division site by microtubule-dependent transport. Cytoskeleton (Hoboken) 69:973-82
Proctor, Stephen A; Minc, Nicolas; Boudaoud, Arezki et al. (2012) Contributions of turgor pressure, the contractile ring, and septum assembly to forces in cytokinesis in fission yeast. Curr Biol 22:1601-8
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

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